Thermodynamics and Kinetics of Solvent-exposed Lipid Tail Protrusions

Mukarram Tahir, Massachusetts Institute of Technology

We utilize atomistic molecular dynamics simulations to investigate the thermodynamic propensity and kinetics of lipid acyl-chain protrusion into solvent as a function of membrane features like lipid composition, hydration and curvature. Single lipid-tail protrusions are one of several hydrophobic membrane defects that have been implicated in critical biological processes like membrane fusion and, more recently, have also been shown to underpin nano-bio interactions like the fusion of monolayer-protected nanoparticles with lipid bilayers. In this work, we present a number of novel physical insights into these important biological phenomena. By developing a geometric criterion for identifying protrusion incidence, we show that the primary modes of lipid-tail protrusion into solvent are elbow and splay protrusions. Using forward simulations and potential of mean force calculations, we demonstrate that the probability of protrusion is unaffected by lipid type in single-component lipid bilayers, but increases with difference in tail length of constituent lipids in multi-component bilayers. We then present evidence that protrusion incidence is enhanced in the presence of membrane curvature. We also report our observation of a critical membrane hydration level below which protrusions are suppressed and relate this observation to current understanding of biological membrane fusion. We then highlight some of our current efforts to leverage these insights for developing monolayer-protected nanoparticles that can mediate fusion between cellular membranes.

Abstract Author(s): Mukarram A. Tahir, Reid C. Van Lehn, and Alfredo Alexander-Katz