Interaction of Conical Membrane Inclusions: Effect of Lateral Tension

Considering two rigid conical inclusions embedded in a membrane subject to lateral tension, we study the membrane-mediated interaction between these inclusions that originates from the hat-shaped membrane deformations associated with the cones. At non-vanishing lateral tensions, the interaction is found to depend on the orientation of the cones with respect to the membrane plane. The interaction of inclusions of equal orientation is repulsive at all distances between them, while the inclusions of opposite orientation repel each other at small separations, but attract each other at larger ones. Both the repulsive and attractive forces become stronger with increasing lateral tension. This is different from what has been predicted on the basis of the same static model for the case of vanishing lateral tension. Without tension, the inclusions repel each other at all distances independently of their relative orientation. We conclude that lateral tension may induce the aggregation of conical membrane inclusions.Comment: 10 pages (revtech), 5 figures (postscript

Segregation of receptor-ligand complexes in cell adhesion zones: Phase diagrams and role of thermal membrane roughness

The adhesion zone of immune cells, the 'immunological synapse', exhibits characteristic domains of receptor-ligand complexes. The domain formation is likely caused by a length difference of the receptor-ligand complexes, and has been investigated in experiments in which T cells adhere to supported membranes with anchored ligands. For supported membranes with two types of anchored ligands, MHCp and ICAM1, that bind to the receptors TCR and LFA1 in the cell membrane, the coexistence of domains of TCR-MHCp and LFA1-ICAM1 complexes in the cell adhesion zone has been observed for a wide range of ligand concentrations and affinities. For supported membranes with long and short ligands that bind to the same cell receptor CD2, in contrast, domain coexistence has been observed for a rather narrow ratio of ligand concentrations. In this article, we determine detailed phase diagrams for cells adhering to supported membranes with a statistical-physical model of cell adhesion. We find a characteristic difference between the adhesion scenarios in which two types of ligands in a supported membrane bind (i) to the same cell receptor or (ii) to two different cell receptors, which helps to explain the experimental observations. Our phase diagrams fully include thermal shape fluctuations of the cell membranes on nanometer scales, which lead to a critical point for the domain formation and to a cooperative binding of the receptors and ligands.Comment: 23 pages, 6 figure

Lateral diffusion of receptor-ligand bonds in membrane adhesion zones: Effect of thermal membrane roughness

The adhesion of cells is mediated by membrane receptors that bind to complementary ligands in apposing cell membranes. It is generally assumed that the lateral diffusion of mobile receptor-ligand bonds in membrane-membrane adhesion zones is slower than the diffusion of unbound receptors and ligands. We find that this slowing down is not only caused by the larger size of the bound receptor-ligand complexes, but also by thermal fluctuations of the membrane shape. We model two adhering membranes as elastic sheets pinned together by receptor-ligand bonds and study the diffusion of the bonds using Monte Carlo simulations. In our model, the fluctuations reduce the bond diffusion constant in planar membranes by a factor close to 2 in the biologically relevant regime of small bond concentrations.Comment: 6 pages, 5 figures; to appear in Europhysics Letter

Lateral phase separation of confined membranes

We consider membranes interacting via short, intermediate and long stickers. The effects of the intermediate stickers on the lateral phase separation of the membranes are studied via mean-field approximation. The critical potential depth of the stickers increases in the presence of the intermediate sticker. The lateral phase separation of the membrane thus suppressed by the intermediate stickers. Considering membranes interacting with short and long stickers, the effect of confinement on the phase behavior of the membranes is also investigated analytically

Indirect interactions of membrane-adsorbed cylinders

Biological and biomimetic membranes often contain aggregates of embedded or adsorbed macromolecules. In this article, the indirect interactions of cylindrical objects adhering to a planar membrane are considered theoretically. The adhesion of the cylinders causes a local perturbation of the equilibrium membrane shape, which leads to membrane-mediated interactions. For a planar membrane under lateral tension, the interaction is repulsive for a pair of cylinders adhering to the same side of the membrane, and attractive for cylinders adhering at opposite membrane sides. For a membrane in an external harmonic potential, the interaction of adsorbed cylinders is always attractive and increases if forces perpendicular to the membrane act on the cylinders.Comment: 9 pages, 8 figures; typos correcte

Structural variability and concerted motions of the T cell receptor - CD3 complex

We investigate the structural and orientational variability of the membrane-embedded T cell receptor (TCR) - CD3 complex in extensive atomistic molecular dynamics simulations based on the recent cryo-EM structure determined by Dong et al. (2019). We find that the TCR extracellular (EC) domain is highly variable in its orientation by attaining tilt angles relative to the membrane normal that range from 15° to 55°. The tilt angle of the TCR EC domain is both coupled to a rotation of the domain and to characteristic changes throughout the TCR - CD3 complex, in particular in the EC interactions of the C_FG loop of the TCR, as well as in the orientation of transmembrane helices. The concerted motions of the membrane-embedded TCR - CD3 complex revealed in our simulations provide atomistic insights on conformational changes of the complex in response to tilt-inducing forces on antigen-bound TCRs

Particle-based membrane model for mesoscopic simulation of cellular dynamics

We present a simple and computationally efficient coarse-grained and solvent-free model for simulating lipid bilayer membranes. In order to be used in concert with particle-based reaction-diffusion simulations, the model is purely based on interacting and reacting particles, each representing a coarse patch of a lipid monolayer. Particle interactions include nearest-neighbor bond-stretching and angle-bending, and are parameterized so as to reproduce the local membrane mechanics given by the Helfrich energy density over a range of relevant curvatures. In-plane fluidity is implemented with Monte Carlo bond-flipping moves. The physical accuracy of the model is verified by five tests: (i) Power spectrum analysis of equilibrium thermal undulations is used to verify that the particle-based representation correctly captures the dynamics predicted by the continuum model of fluid membranes. (ii) It is verified that the input bending stiffness, against which the potential parameters are optimized, is accurately recovered. (iii) Isothermal area compressibility modulus of the membrane is calculated and is shown to be tunable to reproduce available values for different lipid bilayers, independent of the bending rigidity. (iv) Simulation of two-dimensional shear flow under a gravity force is employed to measure the effective in-plane viscosity of the membrane model, and show the possibility of modeling membranes with specified viscosities. (v) Interaction of the bilayer membrane with a spherical nanoparticle is modeled as a test case for large membrane deformations and budding involved in cellular processes such as endocytosis. The results are shown to coincide well with the predicted behavior of continuum models, and the membrane model successfully mimics the expected budding behavior. We expect our model to be of high practical usability for ultra coarse-grained molecular dynamics or particle-based reaction-diffusion simulations of biological systems

An Effective Membrane Model of the Immunological Synapse

The immunological synapse is a patterned collection of different types of receptors and ligands that forms in the intercellular junction between T Cells and antigen presenting cells (APCs) during recognition. The synapse is implicated in information transfer between cells, and is characterized by different spatial patterns of receptors at different stages in the life cycle of T cells. We obtain a minimalist model that captures this experimentally observed phenomenology. A functional RG analysis provides further insights.Comment: 6 pages, 3 figures, submitted for publicatio

Binding constants of membrane-anchored receptors and ligands depend strongly on the nanoscale roughness of membranes

Cell adhesion and the adhesion of vesicles to the membranes of cells or organelles are pivotal for immune responses, tissue formation, and cell signaling. The adhesion processes depend sensitively on the binding constant of the membrane-anchored receptor and ligand proteins that mediate adhesion, but this constant is difficult to measure in experiments. We have investigated the binding of membrane-anchored receptor and ligand proteins with molecular dynamics simulations. We find that the binding constant of the anchored proteins strongly decreases with the membrane roughness caused by thermally excited membrane shape fluctuations on nanoscales. We present a theory that explains the roughness dependence of the binding constant for the anchored proteins from membrane confinement and that relates this constant to the binding constant of soluble proteins without membrane anchors. Because the binding constant of soluble proteins is readily accessible in experiments, our results provide a useful route to compute the binding constant of membrane-anchored receptor and ligand proteins