Molecular Insights into the Electromechanical Coupling in Membranes and Membrane-Protein Systems

Biological membranes are quasi-two-dimensional bilayer structures consisting of a nonideal mixture of lipids, proteins and carbohydrates. Biological membranes compartmentalize cells and their organelles and preserve the cells from the external environment. Cellular membranes are involved in almost all cellular processes and understanding their structure, properties and function are of paramount importance to unravel their role in biochemical reactions. A hallmark feature of these membranes is that they are made of lipid molecules, and behave as liquid crystals. These lipid molecules are amphipathic in nature and they self-organize to form bilayers. Lipid bilayers have remarkable electrical and mechanical properties. These macroscopic properties originate from the structure of the individual lipids, diversity in composition, and the environmental parameters such as temperature, hydration and electric field. Remarkably, lipid molecules and the resulting macroscopic properties have a significant influence on the structure and function of membrane proteins. It is therefore imperative to investigate the electromechanical properties of lipid bilayers and their interactions with membrane proteins to gain mechanistic insights into cellular processes. In this thesis, we have used atomistic simulations to investigate electromechanics of membranes and membrane-protein systems. In the first study, we have obtained the first atomistic evidence of in-plane polarization undergone by lipid bilayers in the presence of lateral electric field and quantified the in-plane flexoelectric coefficient of lipid bilayers. In the follow-up study, we showed for the first time that external lateral electric field can modulate the gel-to-fluid phase transition temperature of bilayers and the melting temperature of lipid bilayer increases with increase in intensity of external lateral electric field. In the third study, we demonstrated that anionic lipids with small headgroup preferentially solvate potassium (Kv) channels and regulate the gating of these channels. In the fourth study, we have identified an electrostatic coupling between phospholipids and vasoactive intestinal polypeptide receptors, and demonstrated a novel role of lipids in stabilizing the orthosteric binding of ligands into the receptors.Mechanical Engineering, Department o