Lipid- and Cholesterol-Mediated Time-Scale-Specific Modulation of the Outer Membrane Protein X Dynamics in Lipid Bilayers

Membrane protein function fundamentally depends on lipid-bilayer fluidity and the composition of the biological membrane. Although dynamic interdependencies between membrane proteins and the surrounding lipids are suspected, a detailed description is still missing. To uncover lipid-modulated membrane protein backbone dynamics, time-scale-specific NMR relaxation experiments with residue-resolution were recorded. The data revealed that lipid order, modified either biochemically or biophysically, changes the dynamics of the immersed membrane protein in a specific and time-scale-dependent manner. A temperature-dependent dynamics analysis furthermore suggests a direct coupling between lipid and protein dynamics in the picosecond–nanosecond, microsecond, and millisecond time scales, caused by the lipid’s trans–gauche isomerization, the segmental and rotational motion of lipids, and the fluidity of the lipid phase, respectively. These observations provide evidence of a direct modulatory capability of the membrane to regulate protein function through lipid dynamics ranging from picoseconds to milliseconds.