Adaptive Lipid Packing and Bioactivity in Membrane Domains

• DOI: 10.1371/journal.pone.0123930
• Publication Date: 2015-04-23T20:23:15Z
• Authors: Erdinc Sezgin; Theresia Gutmann; Tomasz Buhl; Ron Dirkx; Michal Grzybek; Ünal Coskun; Michele Solimena; Kai Simons; Ilya Levental; Petra Schwille
• Keywords: 0301 basic medicine; Science; Q; Cell Membrane; R; Lipids; Glycosphingolipids; Cell Line; Rats; 03 medical and health sciences; Membrane Microdomains; Medicine; Animals; Research Article

Lateral compositional and physicochemical heterogeneity is a ubiquitous feature of cellular membranes on various length scales, from molecular assemblies to micrometric domains. Segregated lipid domains of increased local order, referred to as rafts, are believed to be prominent features in eukaryotic plasma membranes; however, their exact nature (i.e. size, lifetime, composition, homogeneity) in live cells remains difficult to define. Here we present evidence that both synthetic and natural plasma membranes assume a wide range of lipid packing states with varying levels of molecular order. These states may be adapted and specifically tuned by cells during active cellular processes, as we show for stimulated insulin secretion. Most importantly, these states regulate both the partitioning of molecules between coexisting domains and the bioactivity of their constituent molecules, which we demonstrate for the ligand binding activity of the glycosphingolipid receptor GM1. These results confirm the complexity and flexibility of lipid-mediated membrane organization and reveal mechanisms by which this flexibility could be functionalized by cells.