Dr Richard Sear

Reader, Soft Matter Group leader

Academic and research departments

Department of Physics, Soft Matter Group.


University roles and responsibilities

  • Group leader of the Soft Matter group


    Research interests

    My teaching

    My publications


    Dehan Véronique, Bourgeat-Lami Elodie, D'Agosto Franck, Duffy Brendan, Fortini Andrea, Hilton Sharon, Krassa Kalliopi, Keddie Joseph, Koh Ming L., Lansalot Muriel, Lee Michelle, Lesage de la Haye Jennifer, Martin-Fabiani Ignacio, Mantzaridis Christos, Mazeffa Douglas P., Sear Richard, Schulz Malin, Sibbald Morgan, Skerry Brian, Thomas Brett (2017) High-performance water-based barrier coatings for the corrosion protection of structural steel,Steel Construction10(3)pp. 254-259 Ernst und Sohn
    This article provides an overview of the outcomes of a European-funded project called BarrierPlus. A new type of water-based barrier coating was developed for structural steel applications. The advantages of this coating include enhanced moisture resistance, low volatile organic compounds (VOCs) and one-component self-crosslinking free of isocyanates. To enable this performance, a latex polymer binder was uniquely designed without using soap-like molecules, known as surfactants, to form the dispersion. By minimizing surfactants in the coating, the barrier properties were significantly enhanced. The latex was successfully scaled up to 15 kg quantities by an SME, coating formulations were scaled to pilot quantities and a variety of characterization and coating performance tests were completed. A life cycle assessment found that the BarrierPlus coating has a better environmental profile than an industry benchmark solvent-borne coating and showed promising results relative to commercial waterborne benchmarks.
    Sear RP (2002) Distribution of the second virial coefficients of globular proteins, Europhysics Letters60pp. 938-944
    George and Wilson [Acta. Cryst. D 50, 361 (1994)] looked at the distribution of values of the second virial coefficient of globular proteins, under the conditions at which they crystallise. They found the values to lie within a fairly narrow range. We have defined a simple model of a generic globular protein. We then generate a set of proteins by picking values for the parameters of the model from a probability distribution. At fixed solubility, this set of proteins is found to have values of the second virial coefficient that fall within a fairly narrow range. The shape of the probability distribution of the second virial coefficient is Gaussian because the second virial coefficient is a sum of contributions from different patches on the protein surface.
    Mithen JP, Callison AJ, Sear RP (2015) Nucleation of crystals that are mixed composites of all three polymorphs in the Gaussian core model., The Journal of chemical physics142(22)
    We present results of computer simulations of homogeneous crystal nucleation in the Gaussian core model. In our simulations, we study the competition between the body-centered-cubic (bcc), face-centered-cubic (fcc), and hexagonal-close-packed crystal phases. We find that the crystal nuclei that form from the metastable fluid phase are typically "mixed"; they do not consist of a single crystal polymorph. Furthermore, when the fcc phase is stable or fcc and bcc phases are equally stable, this mixed nature is found to persist far beyond the size at the top of the nucleation barrier, that is, far into what would be considered the growth (rather than nucleation) regime. In this region, the polymorph that forms is therefore selected long after nucleation. This has implications. When nucleation is slow, it will be the rate-limiting step for crystallization. Then, the step that determines the time scale for crystallisation is different from the step that controls which polymorph forms. This means that they can be independently controlled. Also between nucleation and polymorph selection, there is a growing phase that is clearly crystalline not fluid, but this phase cannot be assigned to any one polymorph.
    Tavassoli Z, Sear RP (2001) Homogeneous nucleation near a second phase transition and Ostwald's step rule, J. Chemical Physics116pp. 5066-5072
    Homogeneous nucleation of the new phase of one transition near a second phase transition is considered. The system has two phase transitions, we study the nucleation of the new phase of one of these transitions under conditions such that we are near or at the second phase transition. The second transition is an Ising-like transition and lies within the coexistence region of the first transition. It effects the formation of the new phase in two ways. The first is by reducing the nucleation barrier to direct nucleation. The second is by the system undergoing the second transition and transforming to a state in which the barrier to nucleation is greatly reduced. The second way occurs when the barrier to undergoing the second phase transition is less than that of the first phase transition, and is in accordance with Ostwald's rule.
    Sear RP (2008) Continuity of the nucleation of bulk and surface phases,JOURNAL OF CHEMICAL PHYSICS129(16)ARTN 164510 AMER INST PHYSICS
    Sear RP (2004) A model for the accidental catalysis of protein unfolding in vivo, EPL (Europhysics Letters)
    Activated processes such as protein unfolding are highly sensitive to heterogeneity in the environment. We study a highly simplified model of a protein in a random heterogeneous environment, a model of the in vivo environment. It is found that if the heterogeneity is sufficiently large the total rate of the process is essentially a random variable; this may be the cause of the species-to-species variability in the rate of prion protein conversion found by Deleault et al. [Nature, 425 (2003) 717].
    It is well known amongst molecular biologists that proteins with a common ancestor and that perform the same function in similar organisms, can have rather different amino-acid sequences. Mutations have altered the amino-acid sequences without affecting the function; this is called neutral evolution. A simple model of a protein in which the interactions are encoded by sequences of bits is introduced, and used to study how mutations can change these bits, and hence the interactions, while maintaining the stability of the protein solution. This stability is a simple minimal requirement on our model proteins which mimics part of the requirement on a real protein to be functional. The properties of our model protein, such as its second virial coefficient, are found to vary significantly from one model protein to another. It is suggested that this may also be the case for real proteins in vivo.
    Page AJ, Sear RP (2006) Heterogeneous nucleation in and out of pores,PHYSICAL REVIEW LETTERS97(6)ARTN 065701 AMERICAN PHYSICAL SOC
    Sear RP (1997) Theory for polymer coils with necklaces of micelles,Journal of Physics:Condensed Matter10(7)pp. 1677-1686 IOP
    If many micelles adsorb onto the same polymer molecule then they are said to form a necklace. A minimal model of such a necklace is proposed and shown to be almost equivalent to a 1-dimensional fluid with nearest-neighbour interactions. The thermodynamic functions of this fluid are obtained and then used to predict the change in the critical micellar concentration of the surfactant in the presence of the polymer. If the amount of polymer is not too large there are two critical micellar concentrations, one for micelles in necklaces and one for free micelles.
    Proteins must bind to specific other proteins in vivo in order to function. The proteins must bind only to one or a few other proteins of the of order a thousand proteins typically present in vivo. Using a simple model of a protein, specific binding in many component mixtures is studied. It is found to be a demanding function in the sense that it demands that the binding sites of the proteins be encoded by long sequences of bits, and the requirement for specific binding then strongly constrains these sequences. This is quantified by the capacity of proteins of a given size (sequence length), which is the maximum number of specific-binding interactions possible in a mixture. This calculation of the maximum number possible is in the same spirit as the work of Shannon and others on the maximum rate of communication through noisy channels.
    Sear RP (2002) Interfacial tension and nucleation in mixtures of colloids and long ideal polymer coils, Physical Review E65
    Mixtures of ideal polymers with hard spheres whose diameters are smaller than the radius of gyration of the polymer, exhibit extensive immiscibility. The interfacial tension between demixed phases of these mixtures is estimated, as is the barrier to nucleation. The barrier is found to scale linearly with the radius of the polymer, causing it to become large for large polymers. Thus for large polymers nucleation is suppressed and phase separation proceeds via spinodal decomposition, as it does in polymer blends.
    Sear RP (1997) A coil-globule transition of a semiflexible polymer driven by the addition of spherical particles, Phys.Rev. E58pp. 724-728
    The phase behaviour of a single large semiflexible polymer immersed in a suspension of spherical particles is studied. All interactions are simple excluded volume interactions and the diameter of the spherical particles is an order of magnitude larger than the diameter of the polymer. The spherical particles induce a quite long ranged depletion attraction between the segments of the polymer and this induces a continuous coil-globule transition in the polymer. This behaviour gives an indication of the condensing effect of macromolecular crowding on DNA.
    Sear RP (2000) Nucleation of a non-critical phase in a fluid near a critical point, Journal of Chemical Physics v114pp. 3170-3173
    Phase diagrams of some globular proteins have a fluid-fluid transition as well as a fluid-crystal transition. Homogeneous nucleation of the crystal from the fluid phase near the critical point of the fluid-fluid transition is examined. As the fluid-fluid critical point is approached, the number of molecules in the critical nucleus, the nucleus at the top of the free energy barrier to nucleation, is found to diverge as the isothermal compressibility. This divergence is due to a layer of the fluid phase of width equal to the fluid's correlation length which surrounds the core of the nucleus; the number of molecules in a crystalline environment in the nucleus does not diverge. The free energy barrier to nucleation remains finite but its derivative with respect to the chemical potential is equal to minus the number of molecules in the critical nucleus and so diverges.
    Crystals form via nucleation followed by growth. Often nucleation data are interpreted using the classical theory of nucleation, which is essentially a simple theory for the nucleation of a fluid phase. I characterise this classical theory as making six assumptions; I discuss each assumption in turn. I then review experiments and simulations that find nucleation behaviour that cannot be described by the classical theory. The experiments are on the crystallisation from solution of molecules such as drugs and related molecules, ice and calcium carbonate. The review also covers work on non-classical nucleation in solutions of the protein lysozyme, and work on the fascinating phenomenon of nucleation induced by laser pulses. I hope this review will be of interest to those studying the crystallisation of both molecules and ions from solution. The review aims to advance our understanding of the crucial first step in crystallisation, and to enable researchers studying crystallisation in one system to learn from what others have done in studying analogous phenomena in different systems. © 2012 Institute of Materials, Minerals and Mining and ASM International.
    Sear RP (2005) Formation of a metastable phase due to the presence of impurities, J. Phys.: Condens. Matter17pp. 3997-4004
    Phase transitions into a new phase that is itself metastable are common; instead of the equilibrium phase nucleating a metastable phase does so. When this occurs the system is sometimes said to be obeying Ostwald's rule. We show how this can happen when there are impurities present that reduce the barrier to heterogeneous nucleation of the metastable phase. We do so by studying a Potts lattice model using Monte Carlo simulation. Thus, which phase forms depends not only on the properties of the different phases but also on the impurities present. Understanding why systems obey Ostwald's rule may therefore require a study of the impurities present.
    van Meel JA, Page AJ, Sear RP, Frenkel D (2008) Two-step vapor-crystal nucleation close below triple point, JOURNAL OF CHEMICAL PHYSICS129(20)ARTN 204505 AMER INST PHYSICS
    Asanithi P, Saridakis E, Govada L, Jurewicz I, Brunner EW, Ponnusamy R, Cleaver JAS, Dalton AB, Chayen NE, Sear RP (2009) Carbon-nanotube-based materials for protein crystallization,ACS Applied Materials and Interfaces1(6)pp. 1203-1210
    We report on the first use of carbon-nanotube-based films to produce crystals of proteins. The crystals nucleate on the surface of the film. The difficulty of crystallizing proteins is a major bottleneck in the determination of the structure and function of biological molecules. The crystallization of two model proteins and two medically relevant proteins was studied. Quantitative data on the crystallization times of the model protein lysozyme are also presented. Two types of nanotube films, one made with the surfactant Triton X-100 (TX-100) and one with gelatin, were tested. Both induce nucleation of the crystal phase at supersaturations at which the protein solution would otherwise remain clear; however, the gelatin-based film induced nucleation down to much lower supersaturations for the two model proteins with which it was used. It appears that the interactions of gelatin with the protein molecules are particularly favorable to nucleation. Crystals of the C1 domain of the human cardiac myosin-binding protein-C that diffracted to a resolution of 1.6 Å were obtained on the TX-100 film. This is far superior to the best crystals obtained using standard techniques, which only diffracted to 3.0 Å. Thus, both of our nanotube-based films are very promising candidates for future work on crystallizing difficult-to-crystallize target proteins. © 2009 American Chemical Society.
    Bajanca F, Gonzalez-Perez V, Gillespie SJ, Beley C, Garcia L, Theveneau E, Sear RP, Hughes SM (2015) In vivo dynamics of skeletal muscle Dystrophin in zebrafish embryos revealed by improved FRAP analysis, ELIFE4ARTN e06541 ELIFE SCIENCES PUBLICATIONS LTD
    Sear RP (1997) Scattering from small colloidal particles in a semidilute polymer solution, European Physical Journal B v1pp. 313-317
    The correlations between the segments of a semidilute polymer solution are found to induce correlations in the positions of small particles added to the solution. Small means a diameter much less than the polymer's correlation length. In the presence of polymer the particles behave as if they attracted each other. It is shown how the polymer's correlation length may be determined from a scattering experiment performed on the spheres.
    We consider the nucleation of a crystal phase, on a crystalline surface of a different substance. Sixty years ago, Turnbull and Vonnegut predicted that a crystalline surface is best at inducing nucleation of another crystal when there is a perfect epitaxial match between the two bulk lattices. We use computer simulation to show that this is not quite right. In fact, the crystal lattice of a finite nucleus is strained from that in the bulk, and nucleation is fastest when the surface matches this strained lattice. We also find that the approach of Hillier and Ward predicts when nucleation is epitaxial. © Copyright EPLA, 2014.
    Sear RP (2001) Nucleation of the crystalline phase of proteins in the presence of semidilute non-adsorbing polymer, Journal of Chemical Physics
    Starting from a protein solution which is metastable with respect to the crystalline phase, the effect of adding semidilute non-adsorbing polymer is considered. It is found to increase the chemical potential of the protein by a few tenths of kT, which may be enough to lower the barrier to nucleation of the crystalline phase by enough to allow crystallisation. It is also shown that assuming that the polymer induces a pairwise additive attraction leads to qualitatively incorrect results.
    Jurewicz I, King AAK, Worajittiphon P, Asanithi P, Brunner EW, Sear RP, Hosea TJC, Keddie JL, Dalton AB (2010) Colloid-Assisted Self-Assembly of Robust, Three-Dimensional Networks of Carbon Nanotubes over Large Areas, MACROMOLECULAR RAPID COMMUNICATIONS31(7)pp. 609-615 WILEY-V C H VERLAG GMBH
    Sear RP (2002) Flory-Huggins theory for athermal mixtures of hard spheres and larger flexible polymers, Physical Review E66
    A simple analytic theory for mixtures of hard spheres and larger polymers with excluded volume interactions is developed. The mixture is shown to exhibit extensive immiscibility. For large polymers with strong excluded volume interactions, the density of monomers at the critical point for demixing decreases as one over the square root of the length of the polymer, while the density of spheres tends to a constant. This is very different to the behaviour of mixtures of hard spheres and ideal polymers, these mixtures although even less miscible than those with polymers with excluded volume interactions, have a much higher polymer density at the critical point of demixing. The theory applies to the complete range of mixtures of spheres with flexible polymers, from those with strong excluded volume interactions to ideal polymers.
    Brunner EW, Jurewicz I, Heister E, Fahimi A, Bo C, Sear RP, Dalton AB, Donovan PJ (2014) Growth and proliferation of human embryonic stem cells on fully synthetic scaffolds based on carbon nanotubes, ACS Applied Materials and Interfaces6(4)pp. 2598-2603
    Here we show an industrially scalable and inexpensive method of fabricating entirely synthetic, non-xenogeneic carbon nanotube-based scaffolds by vacuum filtration for the culture of human embryonic stem cells. We show that controlled exposure of carbon nanotubes to sonication and the amount of energy delivered to the dispersion directly impacts the surface properties, allowing for control over the nanotopography of the resulting carbon nanotube films, which in turn has demonstrable effects upon in vitro human embryonic stem cells cultures. By altering the nanotube processing conditions before film fabrication, it is possible to influence cell adherence, proliferation and colony morphology. Such a tunable surface with capabilities of influencing stem cell behaviors, combined with the ability to slow or speed population doubling times, will provide crucial solutions for achieving applications envisioned by stem cell biologists to assist future industrial and clinical implementation of human embryonic stem cells. © 2014 American Chemical Society.
    Sear RP (2005) The cytoplasm of living cells: a functional mixture of thousands of components, JOURNAL OF PHYSICS-CONDENSED MATTER17(45)pp. S3587-S3595 IOP PUBLISHING LTD
    Sear RP (1998) The stability limit of polydisperse sticky hard spheres,
    It has been shown by Stell [J. Stat. Phys. 63, 1203 (1991)] that at low temperature monodisperse sticky spheres collapse to form coexisting close-packed solid and infinitely dilute gases. We show that polydisperse sticky spheres also collapse and calculate the collapse temperature. The polydisperse spheres separate into fractions with narrower polydispersities which can then solidify. This is the first example of a single-peaked polydisperse mixture phase separating. It implies that a mixture of polydisperse large hard spheres with much smaller hard spheres does not show fluid--fluid coexistence.
    Sear RP, Pagonabarraga I, Flaus A (2015) Life at the mesoscale: The self-organised cytoplasm and nucleoplasm, BMC Biophysics8(1)
    © 2015 Sear et al.The cell contains highly dynamic structures exploiting physical principles of self-organisation at the mesoscale (100 nm to 10 ¼m). Examples include non-membrane bound cytoplasmic bodies, cytoskeleton-based motor networks and multi-scale chromatin organisation. The challenges of mesoscale self-organisation were discussed at a CECAM workshop in July 2014. Biologists need approaches to observe highly dynamic, low affinity, low specificity associations and to perturb single structures, while biological physicists and biomathematicians need to work closely with biologists to build and validate quantitative models. A table of terminology is included to facilitate multidisciplinary efforts to reveal the richness and diversity of mesoscale cell biology.
    Keddie JL, Andrei DC, Sear RPL, Yeates SG (1999) Surface flattening of thermosetting powder coatings: Theory and experiment., ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY218pp. U626-U626 AMER CHEMICAL SOC
    Sear RP (2006) On the interpretation of quantitative experimental data on nucleation rates using classical nucleation theory, JOURNAL OF PHYSICAL CHEMISTRY B110(43)pp. 21944-21949 AMER CHEMICAL SOC
    Sear RP (2014) Quantitative studies of crystal nucleation at constant supersaturation: Experimental data and models, CrystEngComm16(29)pp. 6506-6522
    Crystallisation starts off with nucleation, which is rather poorly understood. However, over the last few years there have been important quantitative experiments at constant supersaturation, and the modelling of this data has also advanced. Experiments in which the supersaturation is varying, e.g., those at constant cooling rate, are important but hard to interpret. This review focuses on the state of the art in quantitative studies of nucleation at constant supersaturation. We can now test reliably for heterogeneous nucleation and somewhat less reliably for the rarer case of homogeneous nucleation. In the case of heterogeneous nucleation, we can also obtain at least some information on what is responsible for nucleation. We also now have (unfortunately currently untested) predictions for the scaling of nucleation timescales with system size. These predictions may prove important both for scaling up from small droplets to larger volumes, and for scaling down to crystallisation at the nanoscales relevant for nanotechnology applications. Finally, it is worth noting that in many experiments the dynamic range of nucleation times is too large to be measured. This is presumably due to highly variable impurities, and this problem may need to be addressed in future work. This journal is © the Partner Organisations 2014.
    Sear RPL, Mithen JP (2016) A State Between Liquid and Crystal: Locally Crystalline but with the Structure Factor of a Liquid,Crystal Growth and Design16(6)pp. 3049-3053 ACS
    Using computer simulations, we study a nonequilibrium state with a liquid-like S(k) but where over 95% of the molecules are in locally crystalline environments. Due to its liquid-like S(k) and slow dynamics, the state is apparently amorphous, although it contains nanocrystalline order. This nanocrystalline order can strongly bias the polymorph that forms when the state crystallizes.
    First order phase transitions proceed via nucleation. The rate of nucleation varies exponentially with the free-energy barrier to nucleation, and so is highly sensitive to variations in this barrier. In practice, very few systems are absolutely pure, there are typically some impurities present which are rather poorly characterised. These interact with the nucleus, causing the barrier to vary, and so must be taken into account. Here the impurity-nucleus interactions are modelled by random variables. The rate then has the same form as the partition function of Derrida's Random Energy Model, and as in this model there is a regime in which the behaviour is non-self-averaging. Non-self-averaging nucleation is nucleation with a rate that varies significantly from one realisation of the random variables to another. In experiment this corresponds to variation in the nucleation rate from one sample to another. General analytic expressions are obtained for the crossover from a self-averaging to a non-self-averaging rate of nucleation.
    Sear RP (2015) Liquids that form due to dynamics of the molecules that depend on the local density,
    RNA molecules in living cells form what look like liquid droplets formed by liquid/liquid phase separation. But unlike the molecules in conventional phase separating mixtures, RNA molecules are transported by molecular motors that consume energy and so are out of equilibrium. Motivated by this we consider what sort of simple rules for the dynamics of model mRNA molecules lead to liquid/liquid phase separation. We find that dynamics that slow as the local density of molecules increases, drive the formation of liquids. We also look at the analogous separation of the two blocks of a block copolymer, in which the monomers of one block have dynamics that depend on the local density of monomers of that block. We find that this block condenses and separates from the monomers of the other block. This is a simple model of the out-of-equilibrium domain formation found in the chromatin in the nucleus of cells.
    Keddie JL, Ekanayake P, Koenig AM, Weerakkody TG, Barber N, Johannsmann D, Sear RP, McDonald PJ (2007) Influence of the colloidal stability of latex particles on their distribution in drying films, ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY234 AMER CHEMICAL SOC
    Homogeneous nucleation of a new phase near an Ising-like critical point of another phase transition is studied. A scaling analysis shows that the free energy barrier to nucleation contains a singular term with the same scaling as the order parameter associated with the critical point. The total magnetisation of the nucleus scales as the response function and so it diverges. Vapour-liquid critical points are in the Ising universality class and so our results imply that near such a critical point the number of molecules in a nucleus of a another phase, such as a crystalline phase, diverges as the isothermal compressibility. The case where symmetry prevents coupling between the nucleus and the order parameter is also considered.
    Sear RP (1999) Fluid-fluid transitions of hard spheres with a very short-range attraction, Physical Review E v61pp. 6019-6022
    Hard spheres with an attraction of range a tenth to a hundredth of the sphere diameter are constrained to remain fluid even at densities when monodisperse particles at equilibrium would have crystallised, in order to compare with experimental systems which remain fluid. They are found to have a fluid-fluid transition at high density. As the range of the attraction tends to zero, the density at the critical point tends towards the random-close-packing density of hard spheres.
    Sear RP (2000) Molecular dynamics of a dense fluid of polydisperse hard spheres, Journal of Chemical Physics v113pp. 4732-4739
    Slow dynamics in a fluid are studied in one of the most basic systems possible: polydisperse hard spheres. Monodisperse hard spheres cannot be studied as the slow down in dynamics as the density is increased is preempted by crystallisation. As the dynamics slow they become more heterogeneous, the spread in the distances traveled by different particles in the same time increases. However, the dynamics appears to be less heterogeneous than in hard-sphere-like colloids at the same volume fraction. The particles which move least far in a characteristic relaxation time and, particularly, the particles which move farthest in the same time are clustered, not randomly distributed throughout the sample. We study the dynamics at three different widths of the distribution of diameters of the hard spheres. For each width, the relaxation time is the same function of the compressibility factor, suggesting that this determines the relaxation time for hard spheres.
    Liu D, Abdullah CAC, Sear RP, Keddie JL (2010) Cell adhesion on nanopatterned fibronectin substrates,SOFT MATTER6(21)pp. 5408-5416 ROYAL SOC CHEMISTRY
    Biominerals are typically composites of hard matter such as calcite, and soft matter such as proteins. There is currently considerable interest in how the soft matter component is incorporated into the hard matter component. This would typically be a protein that does not fold up into a single rigid domain but is closer to a simple polymer, being incorporated into a growing inorganic crystal in aqueous solution. Here I use computer simulation to study a very simple (2D lattice gas) model of a growing phase and a polymer. This allows me to study the microscopic dynamics of incorporation or rejection of a single polymer by the growing phase. It also allows me to look at how high concentrations of absorbing polymer can both arrest crystal growth, and change the shape of crystals. I find that the incorporation of a single polymer into the growing phase is due to slow dynamics of the polymer at the growth front. These slow dynamics are then unable to keep up with the advancing growth front. This is an intrinsically far-from-equilibrium process and so occurs even when incorporation is thermodynamically highly unfavourable. During the incorporation process, large polymers create large and deep, but transient, pits in the growth front. © The Royal Society of Chemistry 2012.
    Sear RP (2002) The effects of added salt on the second virial coefficients of the complete proteome of E. coli,Journal of Chemical Physics118(11)pp. 5157-5161 AIP
    Bacteria typically have a few thousand different proteins. The number of proteins with a given charge is a roughly Gaussian function of charge - centred near zero, and with a width around ten (in units of the charge on the proton). We have used the charges on E. coli's proteins to estimate the changes in the second virial coefficients of all its proteins as the concentration of a 1:1 salt is increased. The second virial coefficient has dimensions of volume and we find that on average it decreases by about twice the average volume of a protein when the salt concentration is increased from 0.2 to 1 Molar. The standard deviation of the decrease is of the same order. The consequences of this for the complex mixture of proteins inside an E. coli cell, are briefly discussed.
    Brunner EW, Jurewicz I, Heister E, Fahimi A, Bo C, Sear RP, Donovan PJ, Dalton AB (2014) Growth and proliferation of human embryonic stem cells on fully synthetic scaffolds based on carbon nanotubes., ACS Appl Mater Interfaces6(4)pp. 2598-2603
    Here we show an industrially scalable and inexpensive method of fabricating entirely synthetic, non-xenogeneic carbon nanotube-based scaffolds by vacuum filtration for the culture of human embryonic stem cells. We show that controlled exposure of carbon nanotubes to sonication and the amount of energy delivered to the dispersion directly impacts the surface properties, allowing for control over the nanotopography of the resulting carbon nanotube films, which in turn has demonstrable effects upon in vitro human embryonic stem cells cultures. By altering the nanotube processing conditions before film fabrication, it is possible to influence cell adherence, proliferation and colony morphology. Such a tunable surface with capabilities of influencing stem cell behaviors, combined with the ability to slow or speed population doubling times, will provide crucial solutions for achieving applications envisioned by stem cell biologists to assist future industrial and clinical implementation of human embryonic stem cells.
    Sear RP (2003) Protein crystals and charged surfaces: interactions and heterogeneous nucleation, Physical Review E67
    As proteins typically have charges of around 10, they will interact strongly with charged surfaces. We calculate the electrostatic contribution to the interaction of crystals of protein with charged surfaces. The surfaces repel like-charged crystals and attract oppositely-charged crystals, with free energies which can be easily several kT per protein molecule brought into contact with the surface. This means that oppositely charged surfaces can act as a nucleant, they can induce nucleation of a protein crystal by lowering the free energy barrier to heterogeneous nucleation of the crystal from a dilute solution.
    We present results of computer simulations of crystal nucleation on a crystalline surface, in the Lennard-Jones model. Motivated by the pioneering work of Turnbull and Vonnegut [Ind. Eng. Chem. 44, 1292 (1952)], we investigate the effects of a mismatch between the surface lattice constant and that of the bulk nucleating crystal. We find that the nucleation rate is maximum close to, but not exactly at, zero mismatch. The offset is due to the finite size of the nucleus. In agreement with a number of experiments, we find that even for large mismatches of 10% or more, the formation of the crystal can be epitaxial, meaning that the crystals that nucleate have a fixed orientation with respect to the surface lattice. However, nucleation is not always epitaxial, and loss of epitaxy does affect how the rate varies with mismatch. The surface lattice strongly influences the nucleation rate. We show that the epitaxy observed in our simulations can be predicted using calculations of the potential energy between the surface and the first layer of the nucleating crystal, in the spirit of simple approaches such as that of Hillier and Ward [Phys. Rev. B 54, 14037 (1996)].
    Karakosta E, Jenneson PM, Sear RP, McDonald PJ (2006) Observations of coarsening of air voids in a polymer-highly-soluble crystalline matrix during dissolution,PHYSICAL REVIEW E74(1)ARTN 011504 AMERICAN PHYSICAL SOC
    Chayen NE, Saridakis E, Sear RP (2006) Experiment and theory for heterogeneous nucleation of protein crystals in a porous medium, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA103(3)pp. 597-601 NATL ACAD SCIENCES
    Sear RP (2001) Homogeneous nucleation of a non-critical phase near a continuous phase transition,Physical Review E: Statistical, Nonlinear, and Soft Matter Physics63(6)
    Homogeneous nucleation of a new phase near a second, continuous, transition, is considered. The continuous transition is in the metastable region associated with the first-order phase transition, one of whose coexisting phases is nucleating. Mean-field calculations show that as the continuous transition is approached, the size of the nucleus varies as the response function of the order parameter of the continuous transition. This response function diverges at the continuous transition, as does the temperature derivative of the free energy barrier to nucleation. This rapid drop of the barrier as the continuous transition is approached means that the continuous transition acts to reduce the barrier to nucleation at the first-order transition. This may be useful in the crystallisation of globular proteins.
    Sear RP, Cuesta JA (2003) Instabilities in complex mixtures with a large number of components, Phys. Rev. Lett.91
    Inside living cells are complex mixtures of thousands of components. It is hopeless to try to characterise all the individual interactions in these mixtures. Thus, we develop a statistical approach to approximating them, and examine the conditions under which the mixtures phase separate. The approach approximates the matrix of second virial coefficients of the mixture by a random matrix, and determines the stability of the mixture from the spectrum of such random matrices.
    van Meel JA, Sear RP, Frenkel D (2010) Design Principles for Broad-Spectrum Protein-Crystal Nucleants with Nanoscale Pits,PHYSICAL REVIEW LETTERS105(20)ARTN 205501 AMER PHYSICAL SOC
    Meldrum FC, Sear RP (2008) MATERIALS SCIENCE Now You See Them, SCIENCE322(5909)pp. 1802-1803 AMER ASSOC ADVANCEMENT SCIENCE
    At low temperature, spheres with a very short-ranged attraction exist as a close-packed solid coexisting with an infinitely dilute gas. We find that the ratio of the interfacial tension between these two phases to the thermal energy diverges as the range of the attraction goes to zero. The large tensions when the interparticle attractions are short-ranged may be why globular proteins only crystallise over a narrow range of conditions.
    Sear RP (1997) The coil-globule transition of polymers of long rigid monomers connected by flexible spacers, Journal of Chemical Physics
    A simple model of a polymer with long rigid segments which interact via excluded volume repulsions and short ranged attractions is proposed. The coil-globule transition of this model polymer is strongly first order, the globule is crystalline and the coil which coexists with the globule is swollen. A virial expansion truncated at low order is shown to provide a very poor approximation to the free energy and so a cell theory is used to calculate the free energy of the globule.
    Bushnak IA, Labeed FH, Sear RP, Keddie JL (2010) Adhesion of microorganisms to bovine submaxillary mucin coatings: effect of coating deposition conditions,BIOFOULING26(4)pp. 387-397 TAYLOR & FRANCIS LTD
    Sear RP, Warren PB (2002) On the electrical double layer contribution to the interfacial tension of protein crystals, Journal of Chemical Physics
    We study the electrical double layer at the interface between a protein crystal and a salt solution or a dilute solution of protein, and estimate the double layer's contribution to the interfacial tension of this interface. This contribution is negative and decreases in magnitude with increasing salt concentration. We also consider briefly the interaction between a pair of protein surfaces.
    Sear RP (2008) Nucleation in the presence of slow microscopic dynamics,JOURNAL OF CHEMICAL PHYSICS128(21)ARTN 214513 AMER INST PHYSICS
    Sear RP (2011) Crystal nucleation: In a tight corner., Nat Mater10(11)pp. 809-810
    Sear RP (2006) Interactions in protein solutions, CURRENT OPINION IN COLLOID & INTERFACE SCIENCE11(1)pp. 35-39 ELSEVIER SCIENCE LONDON
    Khatri BS, McLeish TCB, Sear RP (2009) Statistical mechanics of convergent evolution in spatial patterning, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA106(24)pp. 9564-9569 NATL ACAD SCIENCES
    Abdullah CA, Asanithi P, Brunner EW, Jurewicz I, Bo C, Azad CL, Ovalle-Robles R, Fang S, Lima MD, Lepro X, Collins S, Baughman RH, Sear RP, Dalton AB (2011) Aligned, isotropic and patterned carbon nanotube substrates that control the growth and alignment of Chinese hamster ovary cells.,Nanotechnology22(20) Institute of Physics
    Here we culture Chinese hamster ovary cells on isotropic, aligned and patterned substrates based on multiwall carbon nanotubes. The nanotubes provide the substrate with nanoscale topography. The cells adhere to and grow on all substrates, and on the aligned substrate, the cells align strongly with the axis of the bundles of the multiwall nanotubes. This control over cell alignment is required for tissue engineering; almost all tissues consist of oriented cells. The aligned substrates are made using straightforward physical chemistry techniques from forests of multiwall nanotubes; no lithography is required to make inexpensive large-scale substrates with highly aligned nanoscale grooves. Interestingly, although the cells strongly align with the nanoscale grooves, only a few also elongate along this axis: alignment of the cells does not require a pronounced change in morphology of the cell. We also pattern the nanotube bundles over length scales comparable to the cell size and show that the cells follow this pattern.
    Sear RP (1999) Phase behaviour of a simple model of globular proteins, Journal of Chemical Physics v111pp. 4800-4806
    A simple model of globular proteins which incorporates anisotropic attractions is proposed. It is closely related to models used to model simple hydrogen-bonding molecules such as water. Theories for both the fluid and solid phases are presented, and phase diagrams calculated. The model protein exhibits a fluid-fluid transition which is metastable with respect to the fluid-solid transition for most values of the model parameters. This is behaviour often observed for globular proteins. The model offers an explanation of the difficulty observed in crystallising some globular proteins and suggests that some proteins may not have a solid phase at all under all but extreme conditions.
    Sear RP (2000) Phase separation in mixtures of colloids and long ideal polymer coils, Physical Review Letters v86pp. 4696-4699
    Colloidal suspensions with free polymer coils which are larger than the colloidal particles are considered. The polymer-colloid interaction is modeled by an extension of the Asakura-Oosawa model. Phase separation occurs into dilute and dense fluid phases of colloidal particles when polymer is added. The critical density of this transition tends to zero as the size of the polymer coils diverges.
    Che Abdullah CA, Azad CL, Ovalle-Robles R, Fang S, Lima MD, Lepró X, Collins S, Baughman RH, Dalton AB, Plant NJ, Sear RP (2014) Primary liver cells cultured on carbon nanotube substrates for liver tissue engineering and drug discovery applications.,ACS Appl Mater Interfaces6(13)pp. 10373-10380
    Here, we explore the use of two- and three-dimensional scaffolds of multiwalled-carbon nanotubes (MWNTs) for hepatocyte cell culture. Our objective is to study the use of these scaffolds in liver tissue engineering and drug discovery. In our experiments, primary rat hepatocytes, the parenchymal (main functional) cell type in the liver, were cultured on aligned nanogrooved MWNT sheets, MWNT yarns, or standard 2-dimensional culture conditions as a control. We find comparable cell viability between all three culture conditions but enhanced production of the hepatocyte-specific marker albumin for cells cultured on MWNTs. The basal activity of two clinically relevant cytochrome P450 enzymes, CYP1A2 and CYP3A4, are similar on all substrates, but we find enhanced induction of CYP1A2 for cells on the MWNT sheets. Our data thus supports the use of these substrates for applications including tissue engineering and enhancing liver-specific functions, as well as in in vitro model systems with enhanced predictive capability in drug discovery and development.
    Sear RP (2007) Dishevelled: a protein that functions in living cells by phase separating, SOFT MATTER3(6)pp. 680-684 ROYAL SOC CHEMISTRY
    Sear RP (1999) Absence of the liquid phase when the attraction is not pairwise additive, Physical Review E61pp. 651-655
    Recent work on charged colloidal suspensions with very low levels of added salt has suggested that although pairs of the colloidal particles repel, clusters of the particles attract. Motivated by this, we study simple model particles which have many-body attractions. These attractions are generic many-body attractions and are not calculated for any specific colloidal suspension. We find that many-body attractions can stabilise solid phases at low pressures but that the liquid phase is either completely absent from the equilibrium phase diagram or present only within a small region of parameter space
    Sear RP (1997) Polymer induced phase coexistence in systems of lamellar phases,
    The effect of adding nonadsorbing polymer to a lamellar phase of surfactant bilayers is studied theoretically. We find that the polymer produces coexistence between two lamellar phases of different layer spacings. The coexistence region is a closed loop, as in the experiments of Ficheux et al. [J. de Physique II 5 823 (1995)]. Within our model the coexistence is driven by depletion.
    Sear RP (1999) Classical nucleation theory for the nucleation of the solid phase of spherical particles with a short-ranged attraction, Journal of Chemical Physics v111pp. 2001-2007
    Classical nucleation theory is used to estimate the free-energy barrier to nucleation of the solid phase of particles interacting via a potential which has a short-ranged attraction. Due to the high interfacial tension between the fluid and solid phases, this barrier is very large, much larger than in hard spheres. It is divergent in the limit that the range of the attraction tends to zero. We predict an upper limit on nucleation in good agreement with the results of experiments on the crystallisation of proteins.
    Sear RP (2008) Phase separation of equilibrium polymers of proteins in living cells, FARADAY DISCUSSIONS139pp. 21-34 ROYAL SOC CHEMISTRY
    Sear RP (2008) Nucleation of a liquid on aerosol nanoparticles, EPL-EUROPHYS LETT83(6)66002pp. 1-6 EDP SCIENCES
    Nucleation of liquid water in the Earth?s atmosphere occurs via heterogeneous nucleation on aerosol particles. We consider nucleation on both water-insoluble and water-soluble aerosol particles. We find that, for particles of the same radius, nucleation on soluble particles dominates. Soluble particles dissolve in the liquid phase and form a droplet even at coexistence. The radius of this droplet essentially determines the supersaturation at which nucleation occurs: the larger the droplet the smaller the supersaturation required before it nucleates to form the bulk liquid. We find that the supersaturation is best measured by the Kelvin radius, which is the radius of a droplet of pure liquid that coexists with vapour of a given supersaturation. We show that nucleation occurs at a universal value of the ratio between the radius of the droplet at coexistence and the Kelvin radius.
    Sear RP (2009) Nucleation via an unstable intermediate phase,JOURNAL OF CHEMICAL PHYSICS131(7)ARTN 074702 AMER INST PHYSICS
    Sear RP (2002) Heterogeneous nucleation near a metastable vapour-liquid transition: the effect of wetting transitions, J. Physics: Condensed Matter14pp. 3693-3703
    Phase transformations such as freezing typically start with heterogeneous nucleation. Heterogeneous nucleation near a wetting transition, of a crystalline phase is studied. The wetting transition occurs at or near a vapour-liquid transition which occurs in a metastable fluid. The fluid is metastable with respect to crystallisation, and it is the crystallisation of this fluid phase that we are interested in. At a wetting transition a thick layer of a liquid phase forms at a surface in contact with the vapour phase. The crystalline nucleus is then immersed in this liquid layer, which reduces the free energy barrier to nucleation and so dramatically increases the nucleation rate. The variation in the rate of heterogeneous nucleation close to wetting transitions is calculated for systems in which the longest-range forces are dispersion forces.
    Colloidal particles are not simple rigid particles, in general an isolated particle is a system with many degrees of freedom in its own right, e.g., the counterions around a charged colloidal particle.The behaviour of model colloidal particles, with a simple phenomenological model to account for these degrees of freedom, is studied. It is found that the interaction between the particles is not pairwise additive. It is even possible that the interaction between a triplet of particles is attractive while the pair interaction is repulsive. When this is so the liquid phase is either stable only in a small region of the phase diagram or absent altogether.
    Sear RP (1999) Metastability and nucleation in the dilute fluid phase of a simple model of globular proteins,
    The dilute fluid phase of model globular proteins is studied. The model possesses a fluid-fluid transition buried within the fluid-crystal coexistence region, as do some globular proteins. If this fluid-fluid transition is not buried deep inside the fluid-crystal coexistence region the crystalline phase does not nucleate within the dilute fluid. We link this lack of nucleation of the crystal to the interactions in our model and speculate that similar interactions between globular proteins are responsible for the difficulty found in crystallising many globular proteins.
    Sear RP, Cuesta JA (2000) What do emulsification failure and Bose-Einstein condensation have in common?, Europhys. Lett.55
    Ideal bosons and classical ring polymers formed via self-assembly, are known to have the same partition function, and so analogous phase transitions. In ring polymers, the analogue of Bose-Einstein condensation occurs when a ring polymer of macroscopic size appears. We show that a transition of the same general form occurs within a whole class of systems with self-assembly, and illustrate it with the emulsification failure of a microemulsion phase of water, oil and surfactant. As with Bose-Einstein condensation, the transition occurs even in the absence of interactions.
    Sear RP (1998) Phase separation and crystallisation of polydisperse hard spheres, Europhysics Letters44pp. 531-535
    Hard spheres with a polydispersity above approximately 8% are shown to crystallise into two phase-separated solid phases. A polydispersity above 8% is too large to be tolerated by a single solid phase but phase separation produces two fractions with polydispersities sufficiently narrow to allow them to crystallise. It may not be possible to observe this in experiment due to the intervention of a glass transition.
    Sear RP (2006) Heterogeneous and homogeneous nucleation compared: Rapid nucleation on microscopic impurities, JOURNAL OF PHYSICAL CHEMISTRY B110(10)pp. 4985-4989 AMER CHEMICAL SOC
    Che Abdullah CA, Asanithi P, Brunner EW, Sear RP, Dalton AB, Lewis Azad C, Ovalle-Robles R, Lima MD, Lepro X, Collins S, Baughman RH (2010) Cell patterning and alignment on nanostructured isotropic and anisotropic carbon nanotubes substrates, European Cells and Materials20(SUPPL.3)pp. 39-39
    Sear RP (2007) Nucleation at contact lines where fluid-fluid interfaces meet solid surfaces, JOURNAL OF PHYSICS-CONDENSED MATTER19(46)ARTN 466106 IOP PUBLISHING LTD
    Sear RP (1999) Depletion induced demixing in polydisperse mixtures of hard spheres,Physical Review Letters82(21)pp. 4244-4247 American Physical Society
    Polydisperse mixtures are those in which components with a whole range of sizes are present. It is shown that the fluid phase of polydisperse hard spheres is thermodynamically unstable unless the density of large spheres decreases at least exponentially as their size increases. The instability is with respect to the large spheres crystallising out into multiple solid phases.
    González-Pérez V, Schmierer B, Hill CS, Sear RP (2011) Studying Smad2 intranuclear diffusion dynamics by mathematical modelling of FRAP experiments., Integr Biol (Camb)3(3)pp. 197-207 RSC Publishing
    We combine Fluorescence Recovery After Photobleaching (FRAP) experiments with mathematical modelling to study the dynamics inside the nucleus of both the TGF-²-sensitive transcriptional regulator Smad2, and Green-Fluorescent Protein (GFP). We show how combining modelling with bleaching strips of different areas allows a rigorous test of whether or not a protein is moving via diffusion as a single species. As noted recently by others, it is important to consider diffusion during the bleaching process. Neglecting it can cause serious error. Also, it is possible to use the bleaching process itself to provide an extra consistency test to the models predicting the recovery. With our method we show that the dynamics of GFP are consistent with it diffusing as a single species in a uniform environment in which flow is negligible. In contrast, the dynamics of the intracellular signal transducer Smad2 are never consistent with it moving as a single species via simple diffusion in a homogeneous environment without flow. Adding TGF-² slows down the dynamics of Smad2 but even without TGF-², the Smad2 dynamics are influenced by one or more of: association, flow, and inhomogeneity in space of the dynamics. We suggest that the dynamics inside cells of many proteins may be poorly described by simple diffusion of a single species, and that our methodology provides a general and powerful way to test this hypothesis.
    Sear RP (2007) Nucleation: theory and applications to protein solutions and colloidal suspensions, JOURNAL OF PHYSICS-CONDENSED MATTER19(3)ARTN 033101 IOP PUBLISHING LTD
    Recent experimental [Diao et al., J. Am. Chem. Soc. 2011 133, 3756.] and simulation results [Sear, J. Phys. Cond. Matt. 2012 24, 052205.] are not consistent with a nucleation rate that is in the thermodynamic limit. This has consequences, if the rate is not in the thermodynamic limit, the time for nucleation will not necessarily scale as one over system size. Here, I show how to analyze data for nucleation times to test for the existence of a well-defined nucleation rate. I also show how to estimate the scaling of the nucleation time with the number of nucleation sites. The prediction is that the farther the system is from the thermodynamic limit, the more rapidly the nucleation time varies with system size. To make this prediction, I use extreme-value statistics. I also show how nucleation data can be analyzed to extract information on the heterogeneity in the surfaces on which nucleation is occurring. © 2013 American Chemical Society.
    Page AJ, Sear RP (2009) Freezing in the bulk controlled by prefreezing at a surface,PHYSICAL REVIEW E80(3)ARTN 031605 AMER PHYSICAL SOC
    Sear RP (1999) Adsorption of polydisperse polymer chains,Journal of Chemical Physics111(5)pp. 2255-2258 AIP
    The adsorption of polydisperse ideal polymer chains is shown to be sensitive to the large N tail of the distribution of chains. If and only if the number of chains decays more slowly than exponentially then there is an adsorption transition like that of monodisperse infinite chains. If the number decays exponentially the adsorption density diverges continuously at a temperature which is a function of the mean chain length. At low coverages, chains with repulsive monomer--monomer interactions show the same qualitative behaviour
    Sear RP (1997) Depletion driven adsorption of colloidal rods onto a hard wall, Physical Review E
    In a mixed suspension of rods and small polymer coils, the rods adsorb onto a hard wall in contact with the suspension. This adsorption is studied in the low density of rods limit. It is driven by depletion forces and is much stronger for long rods than for spheres. This is shown by means of exact, numerical, calculations and an approximate theory.
    Sear RP (2012) Non-self-averaging nucleation rate due to quenched disorder, JOURNAL OF PHYSICS-CONDENSED MATTER24(5)ARTN 052205 IOP PUBLISHING LTD
    Page AJ, Sear RP (2009) Crystallization Controlled by the Geometry of a Surface, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY131(48)pp. 17550-17551 AMER CHEMICAL SOC
    Utgenannt A, Maspero Ross, Fortini Andrea, Turner R, Florescu Marian, Jeynes Christopher, Kanaras AG, Muskens OL, Sear Richard, Keddie Joseph (2016) Fast Assembly of Gold Nanoparticles in Large-Area 2-D Nanogrids Using a One-Step, Near-Infrared Radiation-Assisted Evaporation Process,ACS Nano10(2)pp. 2232-2242 American Chemical Society
    When fabricating photonic crystals from suspensions in volatile liquids using the horizontal deposition method, the conventional approach is to evaporate slowly to increase the time for particles to settle in an ordered, periodic close-packed structure. Here, we show that the greatest ordering of 10 nm aqueous gold nanoparticles (AuNPs) in a template of larger spherical polymer particles (mean diameter of 338 nm) is achieved with very fast water evaporation rates obtained with near-infrared radiative heating. Fabrication of arrays over areas of a few cm2 takes only seven minutes. The assembly process requires that the evaporation rate is fast relative to the particles? Brownian diffusion. Then a two-dimensional colloidal crystal forms at the falling surface, which acts as a sieve through which the AuNPs pass, according to our Langevin dynamics computer simulations. With sufficiently fast evaporation rates, we create a hybrid structure consisting of a two-dimensional AuNP nanoarray (or ?nanogrid?) on top of a three-dimensional polymer opal. The process is simple, fast and one-step. The interplay between the optical response of the plasmonic Au nanoarray and the microstructuring of the photonic opal results in unusual optical spectra with two extinction peaks, which are analyzed via finite-difference time-domain method simulations. Comparison between experimental and modelling results reveals a strong interplay of plasmonic modes and collective photonic effects, including the formation of a high-order stop band and slow-light enhanced plasmonic absorption. The structures, and hence their optical signatures, are tuned by adjusting the evaporation rate via the infrared power density.
    Fortini Andrea, Martin-Fabiani Ignacio, De La Haye Jennifer Lesage, Dugas Pierre-Yves, Lansalot Muriel, D'Agosto Franck, Bourgeat-Lami Elodie, Keddie Joseph, Sear Richard (2016) Dynamic stratification in drying films of colloidal mixtures,Physical Review Letters116(11) American Physical Society
    In simulations and experiments, we study the drying of films containing mixtures of large and small colloidal particles in water. During drying, the mixture stratifies into a layer of the larger particles at the bottom with a layer of the smaller particles on top. We developed a model to show that a gradient in osmotic pressure, which develops dynamically during drying, is responsible for the segregation mechanism behind stratification.
    Sear Richard (2013) Generalisation of Levine's prediction for the distribution of freezing temperatures of droplets: A general singular model for ice nucleation,Atmospheric Chemistry and Physics13pp. 7215-7223 European Geosciences Union
    Models without an explicit time dependence, called singular models, are widely used for fitting the distribution of temperatures at which water droplets freeze. In 1950 Levine developed the original singular model. His key assumption was that each droplet contained many nucleation sites, and that freezing occurred due to the nucleation site with the highest freezing temperature. The fact that freezing occurs due to the maximum value out of large number of nucleation temperatures, means that we can apply the results of what is called extreme-value statistics. This is the statistics of the extreme, i.e., maximum or minimum, value of a large number of random variables. Here we use the results of extreme-value statistics to show that we can generalise Levine's model to produce the most general singular model possible. We show that when a singular model is a good approximation, the distribution of freezing temperatures should always be given by what is called the generalised extreme-value distribution. In addition, we also show that the distribution of freezing temperatures for droplets of onesize, can be used to make predictions for the scaling of the median nucleation temperature with droplet size, and vice versa.
    Sear RPL, Howard M (2006) Modeling dual pathways for the metazoan spindle assembly checkpoint,PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA103(45)pp. 16758-16763 NATL ACAD SCIENCES
    Using computational modelling, we investigate mechanisms of signal transduction focusing on the spindle assembly checkpoint where a single unattached kinetochore is able to signal to prevent cell cycle progression. This inhibitory signal switches off rapidly once spindle microtubules have attached to all kinetochores. This requirement tightly constrains the possible mechanisms. Here we investigate two possible mechanisms for spindle checkpoint operation in metazoan cells, both supported by recent experiments. The first involves the free diffusion and sequestration of cell-cycle regulators. This mechanism is severely constrained both by experimental fluorescence recovery data and also by the large volumes involved in open mitosis in metazoan cells. Using a simple mathematical analysis and computer simulation, we find that this mechanism can generate the inhibition found in experiment but likely requires a two stage signal amplification cascade. The second mechanism involves spatial gradients of a short-lived inhibitory signal that propagates first by diffusion but then primarily via active transport along spindle microtubules. We propose that both mechanisms may be operative in the metazoan spindle assembly checkpoint, with either able to trigger anaphase onset even without support from the other pathway.
    Sear RPL (2014) Nucleation of a new phase on a surface that is changing irreversibly with time,Physical Review E: Statistical, Nonlinear, and Soft Matter Physics89 American Physical Society
    Nucleation of a new phase almost always starts at a surface. This surface is almost always assumed not to change with time. However, surfaces can roughen, partially dissolve and change chemically with time. Each of these irreversible changes will change the nucleation rate at the surface, resulting in a time-dependent nucleation rate. Here we use a simple model to show that partial surface dissolution can qualitatively change the nucleation process, in a way that is testable in experiment. The changing surface means that the nucleation rate is increasing with time. There is an initial period during which no nucleation occurs, followed by relatively rapid nucleation.
    Makepeace D, Fortini A, Markov A, Locatelli P, Lindsay C, Moorhouse S, Lind R, Sear R, Keddie J (2017) Stratification in Binary Colloidal Polymer Films: Experiment and Simulations,Soft Matter13pp. 6969-6980 Royal Society of Chemistry
    When films are deposited from mixtures of colloidal particles of two different sizes, a diverse range of functional structures can result. One structure of particular interest is a stratified film in which the top surface layer has a composition different than in the interior. Here, we explore the conditions under which a stratified layer of small particles develops spontaneously in a colloidal film that is cast from a binary mixture of small and large polymer particles that are suspended in water. A recent model, which considers the cross-interaction between the large and small particles (Zhou et al., Phys. Rev. Lett. (2017) 118, 108002), predicts that stratification will develop from dilute binary mixtures when the particle size ratio (a), initial volume fraction of small particles (f s), and Péclet number are high. In experiments and Langevin dynamics simulations, we systematically vary a and fs in both dilute and concentrated suspensions. We find that stratified films develop when f s is increased, which is in agreement with the model. In dilute suspensions, there is reasonable agreement between the experiments and the Zhou et al. model. In concentrated suspensions, stratification occurs in experiments only for the higher size ratio a = 7. Simulations using a high Péclet number, additionally find stratification with a = 2, when f s is high enough. Our results provide a quantitative understanding of the conditions under which stratified colloidal films assemble. Our research has relevance for the design of coatings with targeted optical and mechanical properties at their surface.
    Martin-Fabiani I, Fortini Andrea, Lesage de la Haye J, Koh ML, Taylor Spencer, Bourgeat-Lami E, Lansalot M, D?Agosto F, Sear Richard, Keddie Joseph (2016) pH-Switchable Stratification of Colloidal Coatings: Surfaces ?On Demand?,ACS Applied Materials and Interfaces8(50)pp. 34755-34761 American Chemical Society
    Stratified coatings are used to provide properties at a surface, such as hardness or refractive index, which are different from underlying layers. Although time-savings are offered by self-assembly approaches, there have been no methods yet reported to offer stratification on demand. Here, we demonstrate a strategy to create self-assembled stratified coatings, which can be switched to homogenous structures when required. We use blends of large and small colloidal polymer particle dispersions in water that self-assemble during drying because of an osmotic pressure gradient that leads to a downward velocity of larger particles. Our confocal fluorescent microscopy images reveal a distinct surface layer created by the small particles. When the pH of the initial dispersion is raised, the hydrophilic shells of the small particles swell substantially, and the stratification is switched off. Brownian dynamics simulations explain the suppression of stratifi-cation when the small particles are swollen as a result of reduced particle mobility, a drop in the pressure gradient, and less time available before particle jamming. Our strategy paves the way for applications in antireflection films and pro-tective coatings in which the required surface composition can be achieved on demand, simply by adjusting the pH prior to deposition.
    Little LJ, Sear RPL, Keddie JL (2015) Does the gamma Polymorph of Glycine Nucleate Faster? A Quantitative Study of Nucleation from Aqueous Solution,Crystal Growth and Design15(11)pp. 5345-5354 American Chemical Society
    We advance the quantitative study of nucleation by combining the study of hundreds of samples, with statistical tests for reproducibility, and for well-defined nucleation rates. Unlike in most previous work, we find that in the samples that nucleate after the first hour of our experiment the equilibrium glycine polymorph predominates over the alpha form.
    Fortini A, Sear R (2017) Stratification and Size Segregation of Ternary and Polydisperse Colloidal Suspensions during Drying,LANGMUIR33(19)pp. 4796-4805 American Chemical Society
    We investigate the drying process of three-component and polydisperse colloidal suspensions using Brownian dynamics simulations. We have previously reported (Phys. Rev. Lett. 2016, 116, 118301) on the drying of binary mixtures. For binary mixtures, we found that a gradient of colloidal osmotic pressure develops during drying and that this leads to the final film being stratified with a layer of smaller particles on top of a layer of larger particles. Here, we find that stratification by size is very general and also occurs in ternary and polydisperse mixtures. We name the segregation effect colloidal diffusiophoresis. In particular, we show that by changing the composition of a ternary mixture, different stratification morphologies can be achieved and hence the film properties can be tuned. In polydisperse spheres, colloidal diffusiophoresis leads to enrichment in the large particles at the bottom part of the film, whereas the top part is enriched with smaller particles. This segregation means that in the final film, the particle size distribution depends on height. Thus, the properties of the film will then depend on height. We propose a model that predicts a power-law dependence of the phoretic velocity on particle size. Results from the model and simulation show a good agreement
    Little Laurie, King Alice A. K., Sear Richard, Keddie Joseph (2017) Controlling the crystal polymorph by exploiting the time dependence of nucleation rates,Journal of Chemical Physics147(14) AIP Publishing
    Most substances can crystallise into two or more different crystal lattices, called polymorphs. Despite this, there are no systems in which we can quantitatively predict the probability of one competing polymorph forming, instead of the other. We address this problem using large scale (hundreds of events) studies of the competing nucleation of the alpha and gamma polymorphs of glycine. In situ Raman spectroscopy is used to identify the polymorph of each crystal. We find that the nucleation kinetics of the two polymorphs is very different. Nucleation of the alpha polymorph starts off slowly but accelerates, while nucleation of the gamma polymorph starts off fast but then slows. We exploit this difference to increase the purity with which we obtain the gamma polymorph by a factor of ten. The statistics of the nucleation of crystals is analogous to that human mortality, and using a result from medical statistics we show that conventional nucleation data can say nothing about what, if any, are the correlations between competing nucleation processes. Thus we can show that it is impossible to disentangle the competing nucleation processes. We also find that the growth rate and the shape of a crystal depends on when it nucleated. This is new evidence that nucleation and growth are linked.
    Rios de Anda I, Turci F, Sear R, Royall P (2017) Long-Lived Non-Equilibrium Interstitial-Solid-Solutions in Binary Mixtures,Journal of Chemical Physics147 AIP Publishing
    We perform particle resolved experimental studies on the heterogeneous crystallisation process of two component mixtures of hard spheres. The components have a size ratio of 0.39. We compared these with molecular dynamics simulations of homogenous nucleation. We find for both experiments and simulations that the final assemblies are interstitial solid solutions, where the large particles form crystalline close-packed lattices, whereas the small particles occupy random interstitial sites. This interstitial solution resembles that found at equilibrium when the size ratios are 0.3 [Filion et al., Phys. Rev. Lett. 107, 168302 (2011)] and 0.4 [Filion, PhD Thesis, Utrecht University (2011)]. However, unlike these previous studies, for our system simulations showed that the small particles are trapped in the octahedral holes of the ordered structure formed by the large particles, leading to long-lived non-equilibrium structures in the time scales studied and not the equilibrium interstitial solutions found earlier. Interestingly, the percentage of small particles in the crystal formed by the large ones rapidly reaches a maximum of 14% for most of the packing fractions tested, unlike previous predictions where the occupancy of the interstitial sites increases with the system concentration. Finally, no further hopping of the small particles was observed.
    Sear R, Warren P (2017) Diffusiophoresis in non-adsorbing polymer solutions: the Asakura-Oosawa model and stratification in drying films,Physical Review E96pp. 062602-1 American Physical Society
    A colloidal particle placed in an inhomogeneous solution of smaller non-adsorbing polymers will move towards regions of lower polymer concentration, in order to reduce the free energy of the interface between the surface of the particle and the solution. This phenomenon is known as diffusiophoresis. Treating the polymer as penetrable hard spheres, as in the Asakura-Oosawa model, a simple analytic expression for the diffusiophoretic drift velocity can be obtained. In the context of drying films we show that diffusiophoresis by this mechanism can lead to stratification under easily accessible experimental conditions. By stratification we mean spontaneous formation of a layer of polymer on top of a layer of the colloid. Transposed to the case of binary colloidal mixtures, this offers an explanation for the stratification observed recently in these systems [A. Fortini et al., Phys. Rev. Lett. 116, 118301 (2016)]. Our results emphasise the importance of treating solvent dynamics explicitly in these problems, and caution against the neglect of hydrodynamic interactions or the use of implicit solvent models in which the absence of solvent back ow results in an unbalanced osmotic force which gives rise to large but unphysical effects.
    Sear Richard (2018) Stratification of mixtures in evaporating liquid films occurs only for a range of volume fractions of the smaller component,Journal of Chemical Physics148(13)134909pp. 134909-1 - 134909-7 AIP Publishing
    I model the drying of a liquid film containing small and big colloid particles. Fortini et al. [A. Fortini et al, Phys. Rev. Lett. 116, 118301 (2016)] studied these films with both computer simulation and experiment. They found that at the end of drying the mixture had stratified with a layer of the smaller particles on top of the big particles. I develop a simple model for this process. The model has two ingredients: arrest of the diffusion of the particles at high density, and diffusiophoretic motion of the big particles due to gradients in the concentration of the small particles. The model predicts that stratification only occurs over a range of initial concentrations of the smaller colloidal species. At concentrations that are either too low or too high, the concentration gradients due to drying are not enough to push the big particles away and so produce a layer at the top of only small particles. In agreement with earlier work, the model also predicts that large Peclet numbers for drying are needed to see stratification.
    Crystallisation by precipitation is a very common technique in industry, however the crystals produced are often of poor quality, characterised by broad particle size distribution and morphological inhomogeneities. These problems can be overcome by the use of ultrasound. Sonocrystallisation, or ultrasound-assisted crystallisation, has already demonstrated its general benefits in terms of reduction in crystallisation time, smaller and more homogeneous crystals and repeatability. However, there are many issues still unaddressed, such as poor knowledge of the mechanism of sonocrystallisation and of the governing parameters of the whole system. This is largely attributed to lack of systematic studies, varying frequency and power while using the same equipment, as well as difficulties in comparing results from different systems. Furthermore, ultrasound is still considered uneconomical in industrial scale, due to its high energy demand. Therefore, there is the necessity of optimising the use of ultrasound for guaranteeing a high-quality product with the lowest energy consumption. This thesis therefore focused on studying the effects of sonocrystallisation for two different crystallisation systems by precipitation: the antisolvent crystallisation of sodium chloride and the reactive crystallisation of ZIF-8, a type of Metal-Organic Frameworks (MOFs). In both systems, frequency, power and sonication time was systematically varied, and the effects on the product obtained investigated. The effect of changing supersaturation was also studied. The comparison between a simpler and a more complex system could help on obtaining general conclusions useful for clarifying the mechanism of sonocrystallisation. The antisolvent sonocrystallisation of sodium chloride revealed that sonication caused a reduction of the crystal size up to 10 times with respect to unsonicated conditions. This was achieved within a few seconds of sonication (5 s for high supersaturation and 15 s for low supersaturation), indicating that the effects of ultrasound were on the nucleation, causing the rapid formation of small and regular crystals. Phenomena of sono-fracture was excluded because the crystals formed were morphologically regular, very different from fragments. Adding a subsequent step in silent conditions or using intermittent ultrasound bursts coupled with silent conditions showed a limited crystal growth. Hence, ultrasound uses the majority of the solute forming new small crystals and leaving in the solution only a small amount of sodium chloride. The effects of different frequencies and powers were more evident at lower supersaturations, with lower frequency being more effective at reducing crystal size. However, under these conditions, although a small average crystal size was obtained, the particle size distributions were bimodal at low power. At high supersaturation, this bimodality disappeared even at low powers. For the reactive crystallisation of ZIF-8 at high excess of ligand, it was confirmed that the action of ultrasound caused a reduction of the crystal size up to nanometre. Furthermore, it was demonstrated again that the action of sonication was on the early stages of the crystallisation. However, the effects of ultrasound resembled a lot the results obtained when only mixing was applied, suggesting that sonication was not directly influencing the chemistry of the reaction. In addition, the BET surface area appeared to be related to the power used, reaching a maximum and decreasing beyond a certain power. This suggests that a competition between micromixing, causing an increase of the BET surface area, and shockwaves, responsible of breaking the framework during its formation. On the other hand, when a low excess of ligand was used, it was revealed that the formation of by-products was accelerated when mixing or sonication were applied. However, if shorter reaction time was applied, it was possible to obtain a reasonable quality of ZIF-8 at low
    Nalesso Silvia, Bussemaker Madeleine J, Sear Richard P, Hodnett Mark, Lee Judy (2018) Development of sodium chloride crystal size during antisolvent crystallization under different sonication modes,Crystal Growth & Design19(1)pp. 141-149 American Chemical Society
    This paper reports for the first time the development in the size and shape of sodium chloride crystals during the anti-solvent crystallization in ethanol under different sonication modes. Sonication using 98 kHz and calorimetric power of 6 W was applied either continuously for a range of crystallisation times (5 ? 90 s) or intermittently (5 s pulse). Under silent conditions, crystallization time of 90 s generated crystals with an average size of 73.8 ± 6.9 ¼m, compared to 8.7 ± 2.8 ¼m under 90 s of continuous sonication. However, it was observed that within the first 5 s of sonication at the beginning of the crystallization, the average crystal size was already reduced to 7.0 ± 3.3 ¼m. If the system was left to crystallise further to 90 s without ultrasound, the crystal size grew only slightly to 8.2 ± 1.4 ¼m. When 5 s burst of ultrasound was applied during the crystallization process, a bimodal distribution of small (from sonication) and large crystals (from the silent period) was obtained. These results imply that the major influence of sonication is crystal nucleation rather than fragmentation, and equilibrium is reached with 5 s sonication by precipitating most of the crystals in solution.
    The more we learn about the cytoplasm of cells, the more we realise that the cytoplasm is not uniform but instead is highly inhomogeneous. In any inhomogeneous solution, there are concentration gradients, and particles move either up or down these gradients due to a mechanism called diffusiophoresis. I estimate that inside metabolically active cells, the dynamics of particles can be strongly accelerated by diffusiophoresis, provided that they are at least tens of nanometres across. The dynamics of smaller objects, such as single proteins are largely unaffected.
    Nalesso Silvia, Bussemaker Madeleine J., Sear Richard P., Hodnett Mark, Lee Judy (2019) A Review on Possible Mechanisms of Sonocrystallisation in Solution,Ultrasonics Sonochemistry Elsevier
    Sonocrystallisation is the application of ultrasound to the crystallisation process. The benefits obtained by sonication have been widely studied since the beginning of the 20th century and so far it is clear that ultrasound can be a very useful tool for enhancing crystallisation and controlling the properties of the final product. Crystal size, polymorphs, purity, process repeatability and lower induction time are only some of the advantages of sonocrystallisation. Even though the effects of sonication on crystallisation are quite clear, the physical explanation of the phenomena involved is still lacking. Is the presence of cavitation necessary for the process? Or is only the bubbles surface responsible for enhancing crystallisation? Are the strong local increases in pressure and temperature induced by cavitation the main cause of all the observed effects? Or is it the strong turbulence induced in the system, instead? Many questions still remain and can only be appreciated with an understanding of the complexity behind the individual processes of crystallisation and acoustic cavitation. Therefore, this review will first summarise the theories behind crystallisation and acoustic cavitation, followed by a description of all the current proposed sonocrystallisation mechanisms, and conclude with an overview on future prospects of sonocrystallisation applications.
    Apostolopoulou Virginia, Junius Niels, Sear Richard P., Budayova-Spano Monika (2020) Mixing salts and polyethylene glycol into protein solutions: The effects of diffusion across semipermeable membranes and of convection,Crystal Growth and Design American Chemical Society
    Growing a protein crystal starts by mixing a solution of the protein, with a solution of a precipitant { such as a salt or polyethylene glycol (PEG). Mixing two solutions is a surprisingly complex process, but this complexity has not received much attention by those crystallising proteins, despite crystallisation being notoriously sensitive to solu- tion conditions. We combine experimental data with modelling to improve our ability to predict mixing timescales for conditions typical of protein crystallisation. We look at the effects of convection, and of diffusion through semipermeable membranes. Our experiments are with dialysis chambers, where the crystallisation chamber is separated from a precipitant reservoir by a semipermeable membrane. This membrane slows mixing down by factors that vary from ten for smaller PEG and salts, to a hundred, for dilute larger PEG. This agrees with our model prediction that for larger polymers diffusion through the membrane is sensitive to both molecular weight and concentra- tion. Both salt and PEG solutions are denser than dilute protein solutions, and this drives convection, which accelerates mixing. Convection is ow due to gravity acting on mass density differences. We show how to determine when convection occurs, and how to estimate its effect on mixing times.
    Williams Ian, Lee Sangyoon, Apriceno Azzurra, Sear Richard P., Battaglia Giuseppe (2020) Diffusioosmotic and convective flows induced by a non-electrolyte concentration gradient,Proceedings of the National Academy of Sciences National Academy of Sciences
    Glucose is an important energy source in our bodies, and its consumption results in gradients over lengthscales ranging from the sub-cellular to entire organs. Concentration gradients can drive material transport through both diffusioosmosis and convection. Convection arises because concentration gradients are mass density gradients. Diffusioosmosis is fluid flow induced by the interaction between a solute and a solid surface. A concentration gradient parallel to a surface creates an osmotic pressure gradient near the surface, resulting in flow. Diffusioosmosis is well understood for electrolyte solutes, but is more poorly characterised for nonelectrolytes such as glucose. We measure fluid flow in glucose gradients formed in a millimetre-long thin channel, and find that increasing the gradient causes a crossover from diffusioosmosis-dominated to convection-dominated flow. We cannot explain this with established theories of these phenomena which predict that both scale linearly. In our system, the convection speed is linear in the gradient, but the diffusioosmotic speed has a much weaker concentration dependence, and is large even for dilute solutions. We develop existing models and show that a strong surface-solute interaction, a heterogeneous surface and accounting for a concentration-dependent solution viscosity can explain our data. This demonstrates how sensitive non-electrolyte diffusioosmosis is to surface and solution properties and to surface-solute interactions. A comprehensive understanding of this sensitivity is required to understand transport in biological systems on lengthscales from micrometres to millimetres where surfaces are invariably complex and heterogeneous.