Pressure perturbation: A prime tool to study conformational substates and volume fluctuations of biomolecular assemblies

Abstract

Fluctuations within biomolecules dictate a plethora of biological processes and are of great importance in functional studies in molecular biophysics. From shaping the free energy landscape of biomolecules themselves to that of biomolecular interactions, they are also implicated in a number of debilitating pathological diseases, thus generating exigent issues that require in-depth investigation. In this regard, pressure perturbation serves as an important tool to mechanistically explore the causes and effects of fluctuations in biomolecules and biomolecular assemblies. Here, we review the underlying principal action of pressure on biomolecules with emphasis on lipid membranes, proteins, amyloids, and membrane-associated complexes along with some highlighted experiments. We first discuss how pressure affects the structure, phase behavior, and dynamics of lipid membranes of varying complexity. We then review the promising role of this tool to study high-energy conformational and functional substates in proteins and elaborate on the use of pressure modulation to understand protein aggregation and fibrillation phenomena. Finally, we present some recent results using pressure perturbation to explore membrane-associated biomolecular assemblies and uncover membrane-mediated conformational substates of proteins, furnishing unprecedented information on proteo-lipid interactions.