Curvature generation and pressure profile modulation in membrane by lysolipids: insights from coarse-grained simulations

Biophys J. 2009 Oct 21;97(8):2267-76. doi: 10.1016/j.bpj.2009.07.051.

Abstract

Although many membrane additives are known to modulate the activities of membrane proteins via perturbing the properties of lipid membrane, the underlying mechanism is often not precisely understood. In this study, we investigate the impact of asymmetrically incorporating single-tailed lysophosphatidylcholine (LPC) into a membrane bilayer using coarse-grained molecular dynamics simulations. Using a simple computational protocol designed to approximately mimic a micropipette setting, we show that asymmetric incorporation of LPC can lead to significant curvature in a bilayer. Detailed analysis of geometrical and mechanical properties (pressure profile) of the resulting mound structure indicates that the degree of pressure profile perturbation is determined not by the local curvature per se but by the packing of lipid headgroups (i.e., area-per-lipid). The findings help provide a concrete basis for understanding the activation mechanism of mechanosensitive channels by asymmetric incorporation of LPC into membrane patches in patch-clamp experiments. The calculated local pressure profiles are valuable to the construction of realistic membrane models for the analysis of mechanosensation in a continuum mechanics framework.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Cholesterol / chemistry
  • Computer Simulation*
  • Lipid Bilayers / chemistry*
  • Lysophosphatidylcholines / chemistry*
  • Membrane Transport Proteins / chemistry
  • Models, Biological*
  • Phosphatidylcholines / chemistry*
  • Pressure*
  • Surface Tension
  • Temperature
  • Video Recording

Substances

  • Lipid Bilayers
  • Lysophosphatidylcholines
  • Membrane Transport Proteins
  • Phosphatidylcholines
  • Cholesterol
  • 1,2-oleoylphosphatidylcholine