Rivalry of cholesterol and antimicrobial peptides as seen by molecular simulations and NMR spectroscopy

Cholesterol Stiffening of Lipid Membranes

“…Future extension to membranes with varying degrees of lipid unsaturation or multicomponent lipid mixtures can inform differences in the mechanical response of asymmetric lipid membranes or domain-forming (raft-like) bilayers (Brown and London 1998 ; Simons and Gerl 2010 ). Because of the abundance of cholesterol in eukaryotic cellular membranes, these studies take on importance with regard to the actions of cholesterol in disorders of lipid metabolism associated with cardiovascular disease, cancer, and dysfunctions of G-protein–coupled receptors (GPCRs) and ion channels, as well the selective actions of antimicrobial peptides (Doole et al 2022 ). In turn, biophysical properties due to lipid packing and membrane stiffening may have been selected during the molecular evolution of cholesterol from lanosterol, as recapitulated in its biosynthetic pathway.…”

“…This approach assumes additivity (sum rule) of the partial molar quantities of the components in the liquid-crystalline state ( l d or l o phase) (Jansson et al 1990 , 1992 ; Otten et al 2000 ). Because the tracer lipid is present only in very small amounts, it adequately captures the properties of the host bilayer (Doole et al 2022 ). Notably, the smaller absolute values for the POPC- d 31 tracer lipid in the DOPC bilayer versus saturated lipids like DMPC- d 54 in the absence of cholesterol manifests the greater degrees of freedom of the acyl chains.…”