No abstract

Membrane reshaping is an essential biological process. The chemical composition of lipid membranes determines their mechanical properties, and thus the energetics of their shape. Hundreds of distinct lipid species make up native bilayers, and this diversity complicates efforts to uncover what compositional factors drive membrane stability in cells. Simplifying assumptions, therefore, are used to generate quantitative predictions of bilayer dynamics based on lipid composition. One assumption commonly used is that "per lipid" mechanical properties are both additive and constant---that they are an intrinsic property of lipids independent of the surrounding composition. Related to this, is the assumption that lipid bulkiness, or "shape" determines its curvature preference, independently of context. In this study, all-atom molecular dynamics simulations on three separate multi-lipid systems were used to explicitly test these assumptions, applying methodology recently developed to isolate properties of single lipids or nanometer-scale patches of lipids. The curvature preference of populations of lipid conformations were inferred from their redistribution on a dynamically fluctuating bilayer. Representative populations were extracted by both structural similarity and semi-automated hidden Markov model analysis. The curvature preferences of lipid dimers were then determined and compared to an additive model that combines the monomer curvature prefer- ence of both the individual lipids. In all three systems, we identified conformational subpopulations of lipid dimers that showed non-additive curvature preference, in each case mediated by a special chemical interaction (e.g., hydrogen bonding). Our study highlights the importance of specific chemical interactions between lipids in multicomponent bilayers and the impact of interactions on bilayer stiffness. We identify two mechanisms of bilayer softening: Diffusional softening, which is driven by the dynamic coupling between lipid distributions and membrane undulations, and conformational softening, which is driven by the inter-conversion between distinct dimeric conformations.

Biological membranes exhibit long-range spatial structure in both chemical composition and geometric shape, which gives rise to remarkable physical phenomena and important biological functions. Continuum models that describe these effects play an important role in our understanding of membrane biophysics at large length scales. We review the mathematical framework used to describe both composition and shape degrees of freedom, and present best practices to implement such models in a computer simulation. We discuss in detail two applications of continuum models of cell membranes: the formation of microemulsion and modulated phases, and the effect of membrane-mediated interactions on the assembly of membrane proteins.

Membrane-induced interactions can play a significant role in the spatial distribution of membrane-bound proteins. We develop a model that combines a continuum description of lipid bilayers with a discrete particle model of proteins to probe the emerging structure of the combined membrane-protein system. Our model takes into account the membrane’s elastic behavior, the steric repulsion between proteins, and the quenching of membrane shape fluctuations due to the presence of the proteins. We employ coupled Langevin equations to describe the dynamics of the system. We show that coupling to the membrane induces an attractive interaction among proteins, which may contribute to the clustering of proteins in biological membranes. We investigate the lateral protein diffusion and find that it is reduced due to transient fluctuations in membrane shape.