Protein crowding and lipid complexity influence the nanoscale dynamic organization of ion channels in cell membranes

Sci Rep. 2017 Nov 30;7(1):16647. doi: 10.1038/s41598-017-16865-6.

Abstract

Cell membranes are crowded and complex environments. To investigate the effect of protein-lipid interactions on dynamic organization in mammalian cell membranes, we have performed coarse-grained molecular dynamics simulations containing >100 copies of an inwardly rectifying potassium (Kir) channel which forms specific interactions with the regulatory lipid phosphatidylinositol 4,5-bisphosphate (PIP2). The tendency of protein molecules to cluster has the effect of organizing the membrane into dynamic compartments. At the same time, the diversity of lipids present has a marked effect on the clustering behavior of ion channels. Sub-diffusion of proteins and lipids is observed. Protein crowding alters the sub-diffusive behavior of proteins and lipids such as PIP2 which interact tightly with Kir channels. Protein crowding also affects bilayer properties, such as membrane undulations and bending rigidity, in a PIP2-dependent manner. This interplay between the diffusion and the dynamic organization of Kir channels may have important implications for channel function.

MeSH terms

  • Cell Membrane / chemistry*
  • Cell Membrane / metabolism*
  • Ion Channels / chemistry*
  • Ion Channels / metabolism*
  • Membrane Lipids / chemistry*
  • Membrane Lipids / metabolism*
  • Molecular Conformation
  • Molecular Dynamics Simulation*
  • Structure-Activity Relationship

Substances

  • Ion Channels
  • Membrane Lipids