The ability of colloidal particles to form equilibrium cluster phases under conditions where the particles interact via a potential consisting of a soft long-range repulsion and a shortrange attraction is well documented. 1,2 In this class of systems, the short-range attraction drives cluster formation, whereas the increasing long-range repulsion due to the accumulating charge of the clusters limits their size. After an initial report 3 that demonstrated the existence of such clusters in systems as diverse as concentrated lysozyme solutions at low ionic strength and weakly charged colloids in a low dielectric constant solvent with added nonadsorbing polymers (to induce a short-range attraction via a depletion mechanism), cluster phases have been demonstrated to exist in a large range of colloidal systems. 4À8In particular, the finding that equilibrium clusters may form in protein solutions under appropriate solution conditions has attracted considerable attention due to its potential biological significance in areas such as protein crystallization or protein condensation diseases. 9À16The initial evidence of the existence of clusters in concentrated lysozyme solutions at low ionic strength has been obtained from the rather peculiar small-angle X-ray (SAXS) and small-angle neutron scattering (SANS) pattern obtained for these systems, 3,17 where an analysis of the dependence of the scattering intensity as a function of the magnitude of the scattering vector q clearly reveals the existence of two peaks in the static structure factor S(q). Surprisingly, both the low as well as the high-q peak were found to be almost independent of the volume fraction φ at sufficiently high values of φ. This was subsequently interpreted as the signature of the presence of equilibrium clusters, where the low-q peak was attributed to a clusterÀcluster interaction peak and thus denoted q c , while the high-q peak was thought to reflect the monomerÀ monomer correlations within the cluster and thus denoted q m .This interpretation was subsequently challenged by Shukla et al., 18 who also conducted SANS and SAXS experiments with lysozyme solutions at low ionic strength. On the basis of the fact that they saw a clear shift of the cluster peak position at lower protein volume fractions, they questioned the existence of equilibrium clusters in lysozyme solutions. However, it has already been pointed out that for comparable experimental conditions, the claim of Shukla et al. relied in fact on scattering data that showed no significant differences to the earlier data on which the cluster model had been based.19,20 SAXSABSTRACT: We present a detailed experimental and numerical study of the structural and dynamical properties of salt-free lysozyme solutions. In particular, by combining small-angle X-ray scattering (SAXS) data with neutron spin echo (NSE) and rheology experiments, we are able to identify that an arrest transition takes place at intermediate densities, driven by the slowing down of the cluster motion. Using an effective pair pote...

We show that weak patchy attractions markedly slow down protein diffusion under conditions prevailing in living cells.

We study the equilibrium liquid structure and dynamics of dilute and concentrated bovine eye lens α-crystallin solutions, using small-angle X-ray scattering, static and dynamic light scattering, viscometry, molecular dynamics simulations, and mode-coupling theory. We find that a polydisperse Percus-Yevick hard-sphere liquid-structure model accurately reproduces both static light scattering data and small-angle X-ray scattering liquid structure data from α-crystallin solutions over an extended range of protein concentrations up to 290 mg/mL or 49% vol fraction and up to ca. 330 mg/mL for static light scattering. The measured dynamic light scattering and viscosity properties are also consistent with those of hard-sphere colloids and show power laws characteristic of an approach toward a glass transition at α-crystallin volume fractions near 58%. Dynamic light scattering at a volume fraction beyond the glass transition indicates formation of an arrested state. We further perform event-driven molecular dynamics simulations of polydisperse hard-sphere systems and use mode-coupling theory to compare the measured dynamic power laws with those of hard-sphere models. The static and dynamic data, simulations, and analysis show that aqueous eye lens α-crystallin solutions exhibit a glass transition at high concentrations that is similar to those found in hard-sphere colloidal systems. The α-crystallin glass transition could have implications for the molecular basis of presbyopia and the kinetics of molecular change during cataractogenesis.alpha crystallin | scattering | mode-coupling theory | molecular dynamics | glass transition T he cytoplasm of the tightly packed fiber cells of the eye lens contains concentrated aqueous protein mixtures that have high refractive indexes, while normally remaining clear enough for vision. Lens clarity depends on short-range order between lens proteins (1, 2) and can be disrupted by both protein aggregation and liquid-liquid phase separation in cataract, a leading cause of blindness. At the high protein concentrations of lens cytoplasm, 25-60% by weight in mammals, small changes in interprotein interactions can disrupt transparency. For human lens proteins with cataractogenic point mutations, and for high-concentration lens protein mixtures, protein interaction changes as small as a fraction of thermal energy, k B T, can induce phase separation and thus lead to opacification (3-7).In addition to equilibrium phase transitions, dynamical transitions including glass formation and gelation can also occur at high protein concentrations like those of the eye lens (8, 9). Relatively abrupt viscoelastic changes associated with glass formation or gelation could harden the lens and contribute to presbyopia and could alter cataract formation rates by affecting aggregation and phase separation kinetics.Here we study the equilibrium liquid structure and dynamics of concentrated solutions of eye-lens α-crystallin protein solutions, using small-angle X-ray scattering (SAXS), static light scattering (SLS)...

The globular protein γB-crystallin exhibits a complex phase behavior, where liquid–liquid phase separation characterized by a critical volume fraction ϕc = 0.154 and a critical temperature Tc = 291.8 K coexists with dynamical arrest on all length scales at volume fractions around ϕ ≈ 0.3–0.35, and an arrest line that extends well into the unstable region below the spinodal. However, although the static properties such as the osmotic compressibility and the static correlation length are in quantitative agreement with predictions for binary liquid mixtures, this is not the case for the dynamics of concentration fluctuations described by the dynamic structure factor S(q,t). Using a combination of dynamic light scattering and neutron spin echo measurements, we demonstrate that the competition between critical slowing down and dynamical arrest results in a much more complex wave vector dependence of S(q,t) than previously anticipated.