Curvature and Lipid Clustering within Asymmetric Biologically Relevant Membrane Models

Abstract

Advances in lipidomics are detailing the compositional and dynamic complexity of cell membranes such as leaflet asymmetry, lipid nano-domains, local curvature, lipid diffusion and lipid composition and distribution. These complexities alter how the membrane interacts with proteins and hence have the potential to control the functional behaviour of proteins and it has become clear that the cell membrane does not only act as a barrier but also plays an important role in controlling the function of proteins such as activation of K+ channels by 4,5-bisphosphate phosphatidylinositol (PIP2)[1], the regulation of the epidermal growth factor receptor by the glycolipid GM3[2] and cholesterol modulation of G-protein coupled receptors[3]. Previous computational studies of membrane proteins have generally been limited to symmetric single lipid component bilayers. We have developed an approach to create highly complex asymmetric biologically relevant membrane models allowing us to obtain a better understanding of membrane properties and enabling us to explore functionally important protein-lipid interactions. We explore properties of biological relevant membranes such as nano-domain formation of certain lipid types but also more macroscopic properties such as membrane undulation and curvature in relation to lipids types and lipid clustering. Extending the system dimensions to > 100 nm allow us to explore membrane dynamics on length scales comparable with experimental ones. The simulations indicate stabilization of curved areas by lipid nano-domains and a tight correlation between lipid species and curvature. We will also explore protein properties such as oligomerisation of e.g. signalling receptors in an “in vivo in silico” approach.