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Biomedical subjects

S A Safran

Publications and source records attributed to S A Safran.

At least 19 recordsLinked to original sources
PubMed2006

Active elasticity of gels with contractile cells.

Cells play an active role in the maintenance of mechanical homeostasis within tissues and their response to elastic forces is important for tissue engineering. We predict the collective response of an ensemble of contractile cells in a three-dimensional elastic medium to externally applied strain fields. Motivated by experiment, we model the cells as polarizable force dipoles that change their orientation in response to the local elastic strain. The analogy between the mechanical response of these systems and the dielectric response of polar molecules is used to calculate the elastic response function. We use this analogy to evaluate the average cell orientation, the mean polarization stress, and the effective elastic constants of the material, as a function of the cell concentration and matrix properties.

Animals↗
PubMed2006

Junctions and end-caps in self-assembled non-ionic cylindrical micelles.

Cylindrical micelles are known to exhibit two types of morphologies: branched networks and linear, worm-like (or thread-like) micelles. These structures correspond to two types of topological defects: end-caps and junction points. Although either type of defect increases the micelle energy (when compared to the cylindrical sections), they are stabilized by an increase in the translational (end-caps) or configurational (junctions) entropy. End-caps reduce the length of the cylindrical micelles, resulting in a suspension of linear, worm-like micelles. Y-junction branch points cause the formation of a network structure that may percolate and coexist thermodynamically with a "sol" of finite cylinders with end-caps. In this paper, we review current experimental and theoretical studies of non-ionic cylindrical micelles in aqueous solutions. We focus on single and multicomponent amphiphiles, and consider both small molecules and macromolecules (polymers), in order to identify the driving forces that determine the type of topological 'defect' and the resulting system morphology.

Journal Article↗
PubMed2006

The immunity of polymer-microemulsion networks.

The concept of network immunity, i.e., the robustness of the network connectivity after a random deletion of edges or vertices, has been investigated in biological or communication networks. We apply this concept to a self-assembling, physical network of microemulsion droplets connected by telechelic polymers, where more than one polymer can connect a pair of droplets. The gel phase of this system has higher immunity if it is more likely to survive (i.e., maintain a macroscopic, connected component) when some of the polymers are randomly degraded. We consider the distribution p(sigma) of the number of polymers between a pair of droplets, and show that gel immunity decreases as the variance of p(sigma) increases. Repulsive interactions between the polymers decrease the variance, while attractive interactions increase the variance, and may result in a bimodal p(sigma).

Computer Simulation↗
PubMed2005

Competitive adsorption of amphiphilic molecules and the stability of water-swollen micelles in oil.

Motivated by recent attempts to confine biochemical processes inside water-in-oil microemulsions, we studied the composition and stability of mixed-amphiphile water-swollen micelles in oil from a theoretical point of view. A novel adsorption model demonstrates how the micellar contents (DNA, proteins, etc.) can dramatically affect the composition of the amphiphilic film and the resulting distribution of micelles. Special attention is given to the effect of electrostatic interactions within the micelles as well as between different ones. Since in a low dielectric medium charge fluctuations can lead to long-range intermicellar attractions, we suggest that the presence of amphiphilic polymers in the surfactant film may be needed to stabilize such microemulsions.

Adsorption↗
PubMed2004

Red blood cell membrane fluctuations and shape controlled by ATP-induced cytoskeletal defects.

We show theoretically how adenosine 5'-triphosphate (ATP)-induced dynamic dissociations of spectrin filaments (from each other and from the membrane) in the cytoskeleton network of red blood cells (RBC) can explain in a unified manner both the measured fluctuation amplitude as well as the observed shape transformations as a function of intracellular ATP concentration. Static defects can be induced by external stresses such as those present when RBCs pass through small capillaries. We suggest that the partially freed actin at these defect sites may explain the activation of the CFTR membrane-bound protein and the subsequent release of ATP by RBCs subjected to deformations. Our theoretical predictions can be tested by experiments that measure the correlation between variations in the binding of actin to spectrin, the activity of CFTR, and the amount of ATP released.

Adenosine Triphosphate↗
PubMed2004

Attractive instability of oppositely charged membranes induced by charge density fluctuations.

We predict the conditions under which two oppositely charged membranes show a dynamic, attractive instability. Two layers with unequal charges of opposite sign can repel or be stable when in close proximity. However, dynamic charge density fluctuations can induce an attractive instability and thus facilitate fusion. We predict the dominant instability modes and time scales and show how these are controlled by the relative charge and membrane viscosities. These dynamic instabilities may be the precursors of membrane fusion in systems where artificial vesicles are engulfed by biological cells of opposite charge.

Cell Membrane↗
PubMed2004

Elastic deformations of grafted layers with surface stress.

We calculate the elastic response of thin films grafted to a solid substrate whose upper surface is subject to a stress. This issue is addressed in the context of biological cell adhesion where adhesive junctions consist of a thin layer of proteins grafted to the extracellular matrix and sheared by the cell contractility apparatus. We show that the finite thickness of the layer limits stress-induced deformations to short ranges proportional to the thickness of the film. In addition, we show that the attachment boundary condition creates an effective shear response to surface stresses that couples all the directions, even for fluidlike layers. We predict that perturbations with wavelengths of order of the film thickness induce resonancelike responses for isotropic rubberlike materials or anisotropic media with high shear moduli. We use these results to predict the elastic deformations of a layer of proteins under shear stress and propose that the resulting, polarized elastic response to local surface forces can explain the observed, anisotropic growth of cell-substrate junctions when subject to external stresses.

Algorithms↗
PubMed2004

Temperature dependence of the thermodynamics and kinetics of micellar solutions.

We predict theoretically the thermodynamics and relaxation kinetics of solutions of cylindrical branched micelles. Using a recently developed theory in combination with the experimental data, we explain the unusual, inverted temperature dependence of the phase separation observed in wormlike micelles and dilute microemulsions. We extend the model to treat the temperature dependence of the relaxation kinetics and explain the observations.

Journal Article↗
PubMed2004

Elastic interactions of active cells with soft materials.

Anchorage-dependent cells collect information on the mechanical properties of the environment through their contractile machineries and use this information to position and orient themselves. Since the probing process is anisotropic, cellular force patterns during active mechanosensing can be modeled as anisotropic force contraction dipoles. Their buildup depends on the mechanical properties of the environment, including elastic rigidity and prestrain. In a finite sized sample, it also depends on sample geometry and boundary conditions through image strain fields. We discuss the interactions of active cells with an elastic environment and compare it to the case of physical force dipoles. Despite marked differences, both cases can be described in the same theoretical framework. We exactly solve the elastic equations for anisotropic force contraction dipoles in different geometries (full space, half space, and sphere) and with different boundary conditions. These results are then used to predict optimal position and orientation of mechanosensing cells in soft material.

Animals↗
PubMed2004

Pinning of fluid membranes by periodic harmonic potentials.

We analyze the thermal fluctuations of fluid membranes in the presence of periodic confining harmonic potentials. This is a simple model of the biologically important, inhomogeneous attachment of the cytoskeleton to the external, fluid membrane of the cell. We study a two-dimensional checkerboard potential as well as one-dimensional, sinusoidal and periodic highly localized, delta function potentials. The membranes are described by an energy functional that includes the curvature bending modulus of the membrane and the harmonic external potential. We predict the magnitude of the membrane shape fluctuations. The sinusoidal potentials give a spontaneous surface tension, and an emergent intermediate-range order in the membrane undulations. The delta function potentials induce a renormalization of the curvature modulus, with perfect pinning at the delta potential sites. After spatial averaging, the delta-function potentials also give rise to an effective surface tension. Finally, we compare these results with measurements of the fluctuations of the red-blood cell membrane, which shows the effects of cytoskeleton attachment to the cellular membrane.

Journal Article↗
PubMed2003

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↗
PubMed2003

Slow fluctuations in enhanced Raman scattering and surface roughness relaxation.

We propose an explanation for the recently measured slow fluctuations and "blinking" in the surface-enhanced Raman scattering spectrum of single molecules adsorbed on a silver colloidal particle. We suggest that these fluctuations may be related to the dynamic relaxation of the surface roughness on the nanometer scale and show that there are two classes of roughness with qualitatively different dynamics. The predictions agree with the measurements of surface roughness relaxation. Using a theoretical model for the kinetics of surface roughness relaxation in the presence of charges and optical electrical fields, we predict that the high-frequency electromagnetic field increases both the effective surface tension and the surface diffusion constant and thus accelerates the surface smoothing kinetics and time scale of the Raman fluctuations in a manner that is linear with the laser power intensity, while the addition of salt retards the surface relaxation kinetics and increases the time scale of the fluctuations. These predictions are in qualitative agreement with the Raman experiments.

Journal Article↗
PubMed2003

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗