P B Sunil Kumar

Inspite of the fluid nature and low elastic modulus, membranes play a crucial role in maintaining the structural integrity of the cell. Recent experiments have challenged the passive nature of the membrane as proposed by the classical fluid mosaic model. Experiments indicate that biomembranes of eukaryotic cells may be laterally organized into small nanoscopic domains, called rafts, which are rich in sphingomyelin and cholesterol. It is largely believed that this in-plane organization is essential for a variety of physiological functions such as signaling, recruitment of specific proteins and endocytosis. However, elucidation of the fundamental issues including the mechanisms leading to the formation of lipid rafts, their stability, and their size remain difficult. This has reiterated the importance of understanding the equilibrium phase behavior and the kinetics of fluid multicomponent lipid membranes before attempts are made to find the effects of more complex mechanisms that may be involved in the formation and stability of lipid rafts. Current increase in interest in the domain formation in multicomponent membranes also stems from the experiments demonstrating fluid-fluid coexistence in mixtures of lipids and cholesterol and the success of several computational models in predicting their behavior. Here we review time dependent Ginzburg Landau model, dynamical triangulation Monte Carlo, and dissipative particle dynamics which are some of the methods that are commonly employed. © 2009 The Physical Society of Japan.

Membranes of organelles in the intracellular trafficking pathway continuously undergo recycling through fission and fusion processes. The effect of these recycling processes on the large-scale morphology of organelles is not well understood. Using a dynamically triangulated surface model, we developed a membrane morphology simulator that allows for membrane trafficking, and analyzed the steady state shape of vesicles subjected to such active remodeling. We study a two-component vesicle composed of 1) active species which can have nonzero spontaneous curvature and participate in the recycling and 2) inactive species which do not participate in the recycling. We obtain a plethora of steady state morphologies as a function of the activity rate, spontaneous curvature, and the strength of interaction between species. We observe that morphology changes, as a function of rate of activity, are diametrically opposite for the two signs of the spontaneous curvature, but only have a weak effect on its magnitude. The interplay between the in-plane diffusion, the activity rate, and the spontaneous curvature are shown to determine the vesicle morphology at the steady state. It is shown that the spontaneous curvature and activity inhibits the formation of clusters of active species on the surface. We carry out linear stability analysis of a continuum model and show that the spherical shape of a vesicle is indeed unstable when subjected to active membrane recycling above a certain activity rate.

The bacterial Shiga toxin is composed of an enzymatically active A-subunit, and a receptor-binding homopentameric B-subunit (STxB) that mediates intracellular toxin trafficking. Upon STxB-mediated binding to the glycolipid globotriaosylceramide (Gb3) at the plasma membrane of target cells, Shiga toxin is internalized by clathrin-dependent and independent endocytosis. The formation of tubular membrane invaginations is an essential step in the clathrin-independent STxB uptake process. However, the mechanism by which STxB induces these invaginations has remained unclear. Using a combination of all-atom molecular dynamics and Monte Carlo simulations we show that the molecular architecture of STxB enables the following sequence of events: the Gb3 binding sites on STxB are arranged such that tight avidity-based binding results in a small increment of local curvature. Membrane-mediated clustering of several toxin molecules then creates a tubular membrane invagination that drives toxin entry into the cell. This mechanism requires: (1) a precise molecular architecture of the STxB binding sites; (2) a fluid bilayer in order for the tubular invagination to form. Although, STxB binding to the membrane requires specific interactions with Gb3 lipids, our study points to a generic molecular design principle for clathrin-independent endocytosis of nanoparticles.

Enhanced colloidal transport beyond the limit imposed by diffusion is usually achieved through external fields. Here, we demonstrate the ballistic transport of a colloidal sphere using internal sources of energy provided by an attached active filament. The latter is modeled as a chain of chemo-mechanically active beads connected by potentials that enforce semi-flexibility and self-avoidance. The fluid flow produced by the active beads and the forces they mediate are explicitly taken into account in the overdamped equations of motion describing the colloid-filament assembly. The speed and efficiency of transport depend on the dynamical conformational states of the filament. We characterize these states using filament writhe as an order parameter and identify ones yielding maxima in speed and efficiency of transport. The transport mechanism reported here has a remarkable resemblance to the flagellar propulsion of microorganisms which suggests its utility in biomimetic systems.

We investigate the combined effects of transmembrane proteins and the subjacent cytoskeleton on the dynamics of phase separation in multicomponent lipid bilayers using computer simulations of a particle-based implicit solvent model for lipid membranes with soft-core interactions. We find that microphase separation can be achieved by the protein confinement by the cytoskeleton. Our results have relevance to the finite size of lipid rafts in the plasma membrane of mammalian cells. © 2014 AIP Publishing LLC.

We study the linearized hydrodynamics of a two-component fluid membrane near a repulsive wall, using a model that incorporates curvature-concentration coupling as well as hydrodynamic interactions. This model is a simplified version of a recently proposed one [J.-B. Manneville et al., Phys. Rev. E 64, 021908 (2001)] for nonequilibrium force centers embedded in fluid membranes, such as light-activated bacteriorhodopsin pumps incorporated in phospholipid egg phosphatidyl choline (EPC) bilayers. The pump-membrane system is modeled as an impermeable, two-component bilayer fluid membrane in the presence of an ambient solvent, in which one component, representing active pumps, is described in terms of force dipoles displaced with respect to the bilayer midpoint. We first discuss the case in which such pumps are rendered inactive, computing the mode structure in the bulk as well as the modification of hydrodynamic properties by the presence of a nearby wall. These results should apply, more generally, to equilibrium fluid membranes comprised of two components, in which the effects of curvature-concentration coupling are significant, above the threshold for phase separation. We then discuss the fluctuations and mode structure in the steady state of active two-component membranes near a repulsive wall. We find that proximity to the wall smoothens membrane height fluctuations in the stable regime, resulting in a logarithmic scaling of the roughness even for initially tensionless membranes. This explicitly nonequilibrium result is a consequence of the incorporation of curvature-concentration coupling in our hydrodynamic treatment. This result also indicates that earlier scaling arguments which obtained an increase in the roughness of active membranes near repulsive walls upon neglecting the role played by such couplings may need to be reevaluated. © 2002 The American Physical Society.

We model the stable self-organized patterns obtained in the nonequilibrium steady states of mixtures of molecular motors and microtubules. In experiments [Nédélec, Nature (London) 389, 305 (1997); Surrey, Science 292, 1167 (2001)] performed in a quasi-two-dimensional geometry, microtubules are oriented by complexes of motor proteins. This interaction yields a variety of patterns, including arrangements of asters, vortices, and disordered configurations. We model this system via a two-dimensional vector field describing the local coarse-grained microtubule orientation and two scalar density fields associated to molecular motors. These scalar fields describe motors which either attach to and move along microtubules or diffuse freely within the solvent. Transitions between single aster, spiral, and vortex states are obtained as a consequence of confinement, as parameters in our model are varied. For systems in which the effects of confinement can be neglected, we present a map of nonequilibrium steady states, which includes arrangements of asters and vortices separately as well as aster-vortex mixtures and fully disordered states. We calculate the steady state distribution of bound and free motors in aster and vortex configurations of microtubules and compare these to our simulation results, providing qualitative arguments for the stability of different patterns in various regimes of parameter space. We study the role of crowding or “saturation” effects on the density profiles of motors in asters, discussing the role of such effects in stabilizing single asters. We also comment on the implications of our results for experiments. © 2004 The American Physical Society.

We study, using dissipative particle dynamics simulations, the effect of active lipid flip-flop on model fluid bilayer membranes. We consider both cases of symmetric as well as asymmetric flip-flops. Symmetric flip-flop leads to a steady state of the membrane with an effective temperature higher than that of the equilibrium membrane and an effective surface tension lower than that of the equilibrium membrane. Asymmetric flip-flop leads to transient conformational changes in the membrane in the form of bud or blister formation, depending on the flip rate. © 2008 American Institute of Physics.

The effect of asymmetry in the transbilayer lipid distribution on the dynamics of phase separation in fluid vesicles is investigated numerically. This asymmetry is shown to set a spontaneous curvature for the domains that alter the morphology and dynamics considerably. For moderate tension, the domains are capped and the spontaneous curvature leads to anomalously slow dynamics, as compared to the case of symmetric bilayers. In contrast, in the limiting cases of high and low tensions, the dynamics proceeds toward full phase separation. © 2006 The American Physical Society.

Several microscopic and mesoscale models have been introduced in the past to investigate various phenomena in lipid membranes. Most of these models account for the solvent explicitly. Since in a typical molecular dynamics simulation, the majority of particles belong to the solvent, much of the computational effort in these simulations is devoted for calculating forces between solvent particles. To overcome this problem, several implicit-solvent mesoscale models for lipid membranes have been proposed during the last few years. In the present article, we review an efficient coarse-grained implicit-solvent model we introduced earlier for studies of lipid membranes. In this model, lipid molecules are coarse-grained into short semi-flexible chains of beads with soft interactions. Through molecular dynamics simulations, the model is used to investigate the thermal, structural and elastic properties of lipid membranes. We will also review here few studies, based on this model, of the phase behavior of nanoscale liposomes, cytoskeleton-induced blebbing in lipid membranes, as well as nanoparticles wrapping and endocytosis by tensionless lipid membranes.