Analyzing Lipid Membrane Defects via a Coarse-Grained to Triangulated Surface Map: The Role of Lipid Order and Local Curvature in Molecular Binding.

Lipid packing defects are known to serve as quantitative indicators for protein binding to lipid membranes. This paper presents a protocol for mapping molecular lipid detail onto a triangulated continuum leaflet representation. Besides establishing the desired forward counterpart to the existing inverse TS2CG map, this coarse-grained to triangulated surface (CG2TS) map enables straightforward extraction of the defect characteristics for any membrane geometry found in nature. We have applied our protocol to investigate the role of local curvature and varying lipid packing on the defect constant π. We find that the defect size is greatly influenced by both factors, arguing strongly against the usual assignment of a single defect constant in the case of more realistic membrane conditions. An important discovery is that lipids in the gel phase produce larger defects, or a higher π, in domains of high (local) curvature than the same lipid in a liquid phase of any curvature. This finding suggests that membranes featuring very ordered lipid packing can bind proteins via large defects in curved regions. Finally, we propose a route for estimating defect constants directly from the standard membrane properties. Identifying the precise role of composition, lipid (tail) order, and (local) curvature in defects for the irregular lipid structures that are (temporally) present in many biological processes is instrumental for obtaining fundamental insight as well as for a rational design of membrane binding targets.