The Effects of Walp Peptides on Phase Behavior in Quaternary Lipid Mixtures: A Molecular Dynamics Study

Abstract

Quaternary lipid mixtures containing a high-melting lipid, a nanodomain-inducing low-melting lipid, a macrodomain-inducing low-melting lipid and cholesterol reveal behaviors not observed in ternary mixtures. Through fixing the amounts of high-melting lipid, total low-melting lipid and cholesterol and altering only the relative amounts of the two low-melting lipids, domain size in quaternary mixtures can be finely tuned from nanoscopic to macroscopic, with an intermediate patterned phase morphology. We have previously used extensive coarse grain and atomistic molecular dynamics simulations to study one such quaternary lipid mixture, containing the high-melting lipid DPPC (16:0,16:0-PC), the low-melting lipids PUPC (16:0,18:2-PC) and DUPC (18:2,18:2-PC), and cholesterol. In particular, we quantified the effect of the two low-melting lipids on domain size, alignment, lipid order and lipid tilt. Using those simulations as a control, we are currently evaluating how adding WALP peptides to the quaternary mixture affects the sizes, alignment and properties of coexisting phases using coarse grained molecular dynamics. We examine how these properties are affected by both the length of the WALP peptide as well as their concentration. A main focus of our work is analyzing the extent to which the WALPs alter the onset of large-scale phase separation and domain alignment. The addition of WALP to the quaternary systems makes these simulations some of the most complex and biologically relevant membranes studied to date with molecular dynamics.