Adaptive lipid packing and bioactivity in membrane domains

PLoS One. 2015 Apr 23;10(4):e0123930. doi: 10.1371/journal.pone.0123930. eCollection 2015.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Membrane / metabolism*
  • Cell Membrane / physiology*
  • Glycosphingolipids / metabolism
  • Lipids / physiology*
  • Membrane Microdomains / metabolism*
  • Membrane Microdomains / physiology*
  • Rats

Substances

  • Glycosphingolipids
  • Lipids

Grant support

This work was supported by grants SO818/1-1, SCHW716/7-1 and “Transregio 83” TRR83 TP18 from Deutsche Forschungsgemeinschaft (DFG), German Federal Ministry of Education and Research (BMBF) grant to the German Center for Diabetes Research (DZD e.V.) and Max Planck Society. IL is a CPRIT Scholar for Cancer Research (grant R1215). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.