Decoupling of dipolar and hydrophobic motions in biological membranes

Cells use homeostatic mechanisms to maintain an optimal composition of distinct types of phospholipids in cellular membranes. The hydrophilic dipolar layer at the membrane interface, composed of phospholipid headgroups, regulates the interactions between cell membranes and incoming molecules, nanoparticles, and viruses. On the other hand, the membrane hydrophobic core determines membrane thickness and forms an environment for membrane-bound molecules such as transmembrane proteins. A fundamental open question is to what extent the motions of these regions are coupled and, consequently, how strongly the interactions of lipid headgroups with other molecules depend on the properties and composition of the membrane hydrophobic core. We combine advanced solid-state nuclear magnetic resonance spectroscopy methodology with high-fidelity molecular dynamics simulations to demonstrate how the rotational dynamics of choline headgroups remain nearly unchanged (slightly faster) with incorporation of cholesterol into a phospholipid membrane, contrasting the well known extreme slowdown of the other phospholipid segments. Notably, our results suggest a new paradigm where phospholipid headgroups interact as quasi-freely rotating flexible dipoles at the interface, independent of the properties in the hydrophobic region.