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Biomedical subjects

S A Safran

Publications and source records attributed to S A Safran.

14 recordsLinked to original sources

Entropic phase separation in polymer-microemulsion networks.

We study theoretically a model system of a transient network of microemulsion droplets connected by telechelic polymers and explain recent experimental findings. Despite the absence of any specific interactions between either the droplets or polymer chains, we predict that as the number of polymers per drop is increased, the system undergoes a first-order phase separation into a dense, highly connected phase, in equilibrium with dilute droplets, decorated by polymer loops. The phase transition is purely entropic and is driven by the interplay between the translational entropy of the drops and the configurational entropy of the polymer connections between them. Because it is dominated by entropic effects, the phase behavior of the system is extremely robust and is independent of the detailed properties of either polymers or drops.

Emulsions↗

Initiation and dynamics of hemifusion in lipid bilayers.

One approach to the understanding of fusion in cells and model membranes involves stalk formation and expansion of the hemifusion diaphragm. We predict theoretically the initiation of hemifusion by stalk expansion and the dynamics of mesoscopic hemifusion diaphragm expansion in the light of recent experiments and theory that suggested that hemifusion is driven by intramembrane tension far from the fusion zone. Our predictions include a square-root scaling of the hemifusion zone size on time as well as an estimate of the minimal tension for initiation of hemifusion. Whereas a minimal amount of pressure is evidently needed for stalk formation, it is not necessarily required for stalk expansion. The energy required for tension-induced fusion is much smaller than that required for pressure-driven fusion.

Computer Simulation↗

Thermodynamics and structure of self-assembled networks.

We study a generic model of self-assembling chains that can branch and form networks with branching points (junctions) of arbitrary functionality. The physical realizations include physical gels, wormlike micelles, dipolar fluids, and microemulsions. The model maps the partition function of a solution of branched, self-assembling, mutually avoiding clusters onto that of a Heisenberg magnet in the mathematical limit of zero spin components. As for the calculation of thermodynamic properties as well as the scattering structure factor, the mapping rigorously accounts for all possible cluster configurations, except for closed rings. The model is solved in the mean-field approximation. It is found that despite the absence of any specific interaction between the chains, the presence of the junctions induces an effective attraction between the monomers, which in the case of threefold junctions leads to a first-order reentrant phase separation between a dilute phase consisting mainly of single chains, and a dense network, or two network phases. The model is then modified to predict the structural properties at the mean-field level. Independent of the phase separation, we predict a percolation (connectivity) transition at which an infinite network is formed. The percolation transition partially overlaps with the first-order transition, and is a continuous, nonthermodynamic transition that describes a change in the topology of the system. Our treatment that predicts both the thermodynamic phase equilibria as well as the spatial correlations in the system allows us to treat both the phase separation and the percolation threshold within the same framework. The density-density correlation has the usual Ornstein-Zernicke form at low monomer densities. At higher densities, a peak emerges in the structure factor, signifying the onset of medium-range order in the system. Implications of the results for different physical systems are discussed.

Journal Article↗

Charge fluctuations and counterion condensation.

We predict a condensation phenomenon in an overall neutral system, consisting of a single charged plate and its oppositely charged counterions. Based on the "two-fluid" model, in which the counterions are divided into a "free" and a "condensed" fraction, we argue that for high surface charge, fluctuations can lead to a phase transition in which a large fraction of counterions is condensed. Furthermore, we show that depending on the valence, the condensation is either a first-order or a smooth transition.

Journal Article↗

Elastic interactions of cells.

Biological cells in soft materials can be modeled as anisotropic force contraction dipoles. The corresponding elastic interaction potentials are long ranged (approximately 1/r3 with distance r) and depend sensitively on elastic constants, geometry, and cellular orientations. On elastic substrates, the elastic interaction is similar to that of electric quadrupoles in two dimensions and for dense systems leads to aggregation with herringbone order on a cellular scale. Free and clamped surfaces of samples of finite size introduce attractive and repulsive corrections, respectively, which vary on the macroscopic scale. Our theory predicts cell reorientation on stretched elastic substrates.

Cell Communication↗

Calculation of forces at focal adhesions from elastic substrate data: the effect of localized force and the need for regularization.

Forces exerted by stationary cells have been investigated on the level of single focal adhesions by combining elastic substrates, fluorescence labeling of focal adhesions, and the assumption of localized force when solving the inverse problem of linear elasticity theory. Data simulation confirms that the inverse problem is ill-posed in the presence of noise and shows that in general a regularization scheme is needed to arrive at a reliable force estimate. Spatial and force resolution are restricted by the smoothing action of the elastic kernel, depend on the details of the force and displacement patterns, and are estimated by data simulation. Corrections arising from the spatial distribution of force and from finite substrate size are treated in the framework of a force multipolar expansion. Our method is computationally cheap and could be used to study mechanical activity of cells in real time.

Algorithms↗

Polymer-induced membrane contraction, phase separation, and fusion via Marangoni flow.

Experiments have shown that the depletion of polymer in the region between two apposed (contacting or nearly contacting) bilayer membranes leads to fusion. In this paper we show theoretically that the addition of nonadsorbing polymer in solution can promote lateral contraction and phase separation of the lipids in the outer monolayers of the membranes exposed to the polymer solution, i.e., outside the contact zone. This initial phase coexistence of higher- and lower-density lipid domains in the outer monolayer results in surface tension gradients in the outer monolayer. Initially, the inner layer lipids are not exposed to the polymer solution and remain in their original "unstressed" state. The differential stresses on the bilayers give rise to a Marangoni flow of lipid from the outer monolayers in the "contact zone" (where there is little polymer and hence a uniform phase) to the outer monolayers in the "reservoir" (where initially the surface tension gradients are large due to the polymer-induced phase separation). As a result, the low-density domains of the outer monolayers in the contact zone expose their hydrophobic chains, and those of the inner monolayers, to the solvent and to each other across the narrow water gap, allowing fusion to occur via a hydrophobic interaction. More generally, this type of mechanism suggests that fusion and other intermembrane interactions may be triggered by Marangoni flows induced by surface tension gradients that provide "action at a distance" far from the fusion or interaction zone.

Cell Membrane↗

Fluctuations and ordering in macroion suspensions.

We calculate the static properties of macroion density fluctuations in both bulk and in confined, strongly interacting, macroion suspensions (macroions interact via the Derjaguin-Landau-Verwey-Overbeek potential) in terms of a simple density-functional ansatz. We show how to map a strongly interacting suspension to a weakly interacting one and obtain the renormalized charge, diameter and scattering structure factors analytically. The model is extrapolated to predict crystalline order in terms of a Hansen-Verlet-type of criterion as well as an effective hard-sphere crystallization condition, and good agreement with simulations is found. The increase in correlations observed in recent experiments in two, confined layers is demonstrated.

Journal Article↗

Defect-induced phase separation in dipolar fluids.

A defect-induced, critical phase separation in dipolar fluids is predicted, which replaces the usual liquid-gas transition that is driven by the isotropic aggregation of particles and is absent in dipolar fluids due to strong chaining. The coexisting phases are a dilute gas of chain ends that coexists with a high-density liquid of chain branching points. Our model provides a unified explanation for the branched structures, the unusually low critical temperature and density, and the consequent two-phase coexistence "islands" that were recently observed in experiment and simulation.

Journal Article↗

Pearling in cells: a clue to understanding cell shape.

Gradual disruption of the actin cytoskeleton induces a series of structural shape changes in cells leading to a transformation of cylindrical cell extensions into a periodic chain of "pearls." Quantitative measurements of the pearling instability give a square-root behavior for the wavelength as a function of drug concentration. We present a theory that explains these observations in terms of the interplay between rigidity of the submembranous actin shell and tension that is induced by boundary conditions set by adhesion points. The theory allows estimation of the rigidity and thickness of this supporting shell. The same theoretical considerations explain the shape of nonadherent edges in the general case of untreated cells.

Actins↗

Pressure of correlated layer-charge and counterion fluctuations in charged thin films.

We predict the fluctuation contribution to the interaction between two surfaces with both mobile layer charges and delocalized counterions. The correlation (coupling) between the layer-charge fluctuations and the counterion fluctuations (around a piecewise homogeneous mean-field density profile) is taken into account in the Gaussian approximation. We find that this correlation significantly increases the magnitude of the interlayer fluctuation attraction. The counterion fluctuation pressure is calculated as a function of the intersurface distance and we show how the large and small distance limits correspond to three-dimensional (3D) and 2D fluctuations, respectively. In addition, we predict the charge density-density correlation functions. Experimental implications of the model are discussed.

Journal Article↗

Effect of lipid characteristics on the structure of transmembrane proteins.

The activity of embedded proteins is known to vary with lipid characteristics. Indeed, it has been shown that some cell-membrane proteins cannot function unless certain non-bilayer-forming lipids (i.e., nonzero spontaneous curvature) are present. In this paper we show that membranes exert a line tension on transmembrane proteins. The line tension, on the order of 1-100 kT/protein, varies with the lipid properties and the protein configuration. Thus, membranes composed of different lipids favor different protein conformations. Model predictions are in excellent agreement with the data of Keller et al. (Biophys. J. 1993, 65:23-27) regarding the conductance of alamethicin channels.

Alamethicin↗

Localized dynamic light scattering: a new approach to dynamic measurements in optical microscopy.

We present a new approach to probing single-particle dynamics that uses dynamic light scattering from a localized region. By scattering a focused laser beam from a micron-size particle, we measure its spatial fluctuations via the temporal autocorrelation of the scattered intensity. We demonstrate the applicability of this approach by measuring the three-dimensional force constants of a single bead and a pair of beads trapped by laser tweezers. The scattering equations that relate the scattered intensity autocorrelation to the particle position correlation function are derived. This technique has potential applications for measurement of biomolecular force constants and probing viscoelastic properties of complex media.

Biophysics↗