Deciphering the dynamic interplay of lipids and membrane proteins by High Pressure NMR/modelling – UnderPressure

Lipids and proteins are the main components of cell membranes. Although their mutual interactions and dynamics govern many cell functions, we are still far from a complete description of these interactions. In the UnderPressure project we will exploit and further develop an analytical method that we recently introduced to probe lipid/protein interactions and membrane protein stability. High pressure has proven highly efficient to probe the conformational landscapes of hydrosoluble proteins and the phase behavior of lipid assemblies, and our preliminary data demonstrate that we are now ready to address those challenging binary lipid bilayer/protein systems to benefit from all the power of high pressure. We will combine cutting-edge experimental (lipid nanodiscs and NMR spectroscopy) and computational tools in a tightly integrated interdisciplinary approach to reveal the interplay between lipid and protein dynamics at atomic resolution and over a wide range of timescales. We will study selected membrane proteins with distinct mechanical properties from highly rigid (porin) to highly plastic (G-Protein Coupled Receptor), and determine their conformational stability as well as their impact on lipid dynamics. Reciprocally, we will identify the dynamic modes of the lipid that are transmitted to the membrane protein in term of motion timescale and impact on the protein conformational landscape. The UnderPressure project will establish the methodological basis of the new field of biomembranes under pressure at atomic resolution, with broad impacts on our understanding of protein/lipid dynamics at ambient pressure, and the adaptation of these biomolecules and micro-organisms to high-pressure environments as found in deep-seas. In the industrial world, this newly acquired knowledge will help us understanding the phenomena occurring for example during food processing and pascalization.