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.