P B Sunil Kumar

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.

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.

Rheology of Complex Fluids Abhijit P. Deshpande, J. Murali Krishnan, P. B. Sunil Kumar This book provides an in-depth treatment of complex fluids. A clear understanding of the flow and rheological behavior of such fluids is crucial while carrying out the processing operations, designing equipments which handle/transport these fluids, and in their end-use applications. This book: • Discusses multicomponent-multiphase systems of which most of complex fluids are examples •Covers a wide variety of application areas from polymers to biological systems. •Introduces active fluids, with internal energy generation, and their rheology •Involves multidisciplinary tools, and brings together contributors from different backgrounds Rheology of Complex Fluids is a must-read for researchers and practicing engineers in the complex fluid industry. Selected portions of the book can be used as supplementary teaching material. © Springer Science+Business Media, LLC 2010.

Lipid vesicles are closed two dimensional fluid surfaces that are studied extensively as model systems for understanding the physical properties of biological membranes. Here we review the recent developments in the Monte Carlo techniques for simulating fluid vesicles and discuss some of their applications. The technique, which treats the membrane as an elastic sheet, is most suitable for the study of large scale conformations of membranes. The model can be used to study vesicles with fixed and varying topologies. Here we focus on the case of multi-component membranes with the local lipid and protein composition coupled to the membrane curvature leading to a variety of shapes. The phase diagram is more intriguing in the case of fluid vesicles having an in-plane orientational order that induce anisotropic directional curvatures. Methods to explore the steady state morphological structures due to active flux of materials have also been described in the context of Monte Carlo simulations.

Interaction between similarly charged surfaces can be attractive at high electrostatic coupling constants = lBZ2/μGC, where lB is the Bjerrum length, μGC the Gouy-Chapman length, and Z the valency of counterions. While this effect has been studied previously in detail, as a function of surface charge density and valency of the pointlike counterions, much less is known about the effect of counterion size. We apply the Wang-Landau sampling Monte Carlo (MC) simulation method to compute the free energy F as a function of the scaled distance between the plates D̃ =D/ μGC for a range of and scaled counterion radii R̃ =R/ μGC. We find that for large and small ion radius, there is a global equilibrium distance D̃ = D̃ eq =2 (1+ R̃), correctly giving the expected value at the point counterion limit. With increasing R̃ the global minimum in F(D̃) changes to a metastable state and finally this minimum vanishes when R̃ reaches a critical value, which depends on . We present a state diagram indicating approximate boundaries between these three regimes. The Wang-Landau MC method, as it is applied here, offers a possibility to study a wide spectrum of extended problems, which cannot be treated by the use of contact value theorem. © 2010 American Institute of Physics.

The kinetics of registration of lipid domains in the apposing leaflets of symmetric bilayer membranes is investigated via systematic dissipative particle dynamics simulations. The decay of the distance between the centres of mass of the domains in the apposing leaflets is almost linear during early stages, and then becomes exponential during late times. The time scales of both linear and exponential decays are found to increase with decreasing strength of interleaflet coupling. The ratio between the time scales of the exponential and linear regimes decreases with increasing domain size, implying that the decay of the distance between the domains' centres of mass is essentially linear for large domains. These numerical results are largely in agreement with the recent theoretical predictions of Han and Haataja [Soft Matter, 2013, 9, 2120-2124]. We also found that the domains become elongated during the registration process. © the Partner Organisations 2014.

We demonstrate the existence of a percolationlike stiffness transition in fiber networks with a bidisperse orientation distribution and with fiber densities clearly above the geometrical and the ordinary stiffness transition. The fibers are oriented parallel and perpendicular to a strain direction and they have a large fiber aspect ratio. The stiffness K of the fiber nets can be described by a scaling relation, Kâ̂ταg[(ε- ε c)/τ -β], where τ is the fraction of fibers parallel to strain. g is a scaling function that is roughly described by a power law g(x)â̂xγ for stiffness above the transition and by a constant below the transition. The transition point is characterized by qualitative changes in the distribution of the elastic deformation energy of the fibers, the deformation mode of the fibers, the effective Poisson ratio of the nets, the distribution of elastic energy on fibers and cross links, and the ratio of elastic and viscous dissipation energy. This transition opens the possibility of extreme stiffness variations with minimal mesh manipulations in the vicinity of the transition (i.e., a stiffness gate). It is possible that this transition affects the mechanical behavior of the cytoskeleton in cells. © 2012 American Physical Society.

Based on indirect observations, there currently exists a consensus that the plasma membrane of mammalian cells exhibits nontrivial lateral heterogeneities in the form of nanoscale lipid domains known as lipid rafts which are rich in cholesterol and sphingolipids. Lipid rafts have been implicated in a range of biological functions, including signal transduction, endocytosis, trafficking, virus uptake, and regulation of the membrane tension. The elucidation of the finite size of lipid rafts in the plasma membrane has been a challenging problem since multicomponent lipid vesicles composed of saturated lipid, an unsaturated lipid, and cholesterol also exhibit domains, but these are much larger than the lipid rafts in the plasma membrane. Many computational studies have recently been performed to address the phase separation in multicomponent membranes and potential mechanisms leading to nanoscale phase separation in the plasma membrane. This chapter provides an overview of major computational studies of multicomponent lipid membranes with a particular focus on time-dependent Ginzburg-Landau models, dynamic triangulation Monte Carlo models, coarse-grained molecular dynamics, and dissipative particle dynamics. © 2011 Elsevier Inc.