Mechanical properties of anionic asymmetric bilayers from atomistic simulations

Abstract

Mechanotransduction, the biological response to mechanical stress, is often initiated by the activation of mechanosensitive (MS) proteins upon mechanically induced deformations of the cell membrane. A current challenge to fully understand this process is to predict how lipid bilayers deform upon application of mechanical stress. In this context, it is now well established that anionic lipids influence the function of many proteins. Here, we test the hypothesize that anionic lipids could indirectly modulate MS proteins by alteration of the lipid bilayer mechanical properties. Using all-atom molecular dynamics simulations, we computed the bilayer bending rigidity (K_C), the area compressibility (K_A), and the surface shear viscosity ({\eta}_m) of phosphocholine (PC) lipid bilayers containing or not phosphatidylserine (PS) or phosphatidylinositol bisphosphate (PIP2) at physiological concentrations in the lower leaflet. Tensionless leaflets were first checked for each asymmetric bilayer model, and a formula for embedding an asymmetric channel in an asymmetric bilayer is proposed. Results from two different sized bilayers show consistently that the addition of 20% surface charge in the lower leaflet of PC bilayer by PIP2 has minimal impact on its mechanical properties, while PS reduced the bilayer bending rigidity by 22%. As a comparison, supplementing the PIP2-enriched PC membrane with 30% cholesterol, a known rigidifying steroid lipid, produces a significant increase in all three mechanical constants. Analysis of pairwise splay moduli suggests that the effect of anionic lipids on bilayer bending rigidity largely depends on the number of anionic lipid pairs formed during simulations. The potential implication of bilayer bending rigidity is discussed in the framework of mechanosensitive Piezo channels.