Molecular simulations and NMR reveal how lipid fluctuations affect membrane mechanics.

Abstract

The lipid make-up of a bilayer determines its measurable properties but how the motions of individual molecules combine to produce these properties remains unclear. By exploiting the synergy between NMR spectroscopy and molecular dynamics (MD) simulations, we show that the lipid dynamics in a bilayer are collective yet segmental in nature and contribute directly to bilayer elasticity. Our analysis entails development of a theoretical framework that allows direct comparison of carbon-hydrogen (C-H) bond relaxations as measured by simulations and solid-state NMR experiments. The new formalism allows validation of lipid force fields against NMR data by considering a fixed bilayer normal (director axis) and restricted anisotropic motion of the C-H bonds described by segmental order parameters. The simulations showed that the spin-lattice relaxation rates scale as the squared order parameter of the lipid acyl chains, yielding an apparent bending modulus kc of the bilayer. Our results mirror the experimental observations of kc obtained from solid-state NMR studies of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers with increasing amounts of cholesterol. These findings are further validated by neutron spin-echo measurements of membrane bending fluctuations and emergent elastic properties. Analysis of the thermally excited C-H bond fluctuations from the simulations also reveals collective dynamics of a nematic-like nature and uncovers a critical role of interleaflet coupling in membrane mechanics. This study thus provides novel insights into the inner workings of lipid membranes and establishes a new tool for validating computational approaches against experimental data.