Native Cellular Membranes\nFacilitate Channel Activity\nof MscL by Enhancing Slow Collective Motions of Its Transmembrane\nHelices

Mechanosensitive channels of large conductance (MscL)\nserve as\na mechanoelectrical valve of cells in response to the membrane tension.\nThe influence of membrane environments on the MscL channel activity\nand the underlying mechanism remains unclear. Herein, we developed\na new sample preparation protocol that allows for the detection of\nhigh-quality <sup>1</sup>H-detected solid-state NMR spectra of MscL\nin cellular membranes, enabling site-specific analysis of its dynamics.\nDipolar order parameters and spin relaxation rates are measured for\n51 residues of MscL in synthetic and native membranes. The dynamics\ndata reveal that while MscL maintains a similar rigidity in both membrane\nenvironments, it exhibits enhanced slow collective motions in the\nnative cellular membranes. Molecular dynamics simulations demonstrate\nthe critical role of slow motions in the mechanosensitivity of MscL\nby promoting protein–membrane interactions. This study examines\natomic-resolution dynamics of a membrane–protein in cellular\nmembranes and provides novel insights into the functional significance\nof membrane–protein dynamics.