Deciphering the interaction between lipid membranes and proteins in presence of molecular crowders: An ultrafast vibrational spectroscopic and theoretical study
This proposal outlines a cutting-edge research endeavor aimed at unraveling molecular interactions of lipid membranes in crowded biological environments.
The omnipresence of aqueous solutions in contact with charged surfaces and the critical role of molecular-level details of water–surface interactions with biological macromolecular systems have inspired researchers to explore their profound influence on interfacial functions and properties in natural processes. Biological phenomena inherently occur in crowded, heterogeneous environments, making it essential to account for crowding effects in our understanding of biophysical processes at the molecular level.
My research aims to address a significant knowledge gap: while interactions and dynamics of water molecules near lipid membranes have been extensively studied, a systematic investigation in the presence of diverse crowding agents remains limited in the literature. This proposal seeks to quantify the effects of specific crowding agents and protein concentrations near membranes on ultrafast interfacial hydrogen-bond dynamics using a powerful combination of ultrafast two dimensional infrared spectroscopy, vibrational Stark spectroscopy and complementary molecular dynamics simulations.
This project will be conducted under the mentorship of Dr. Sayan Bagchi at the National Chemical Laboratory, Pune. His pioneering work in ultrafast 2D IR spectroscopy, and my previous research experience on vibrational spectroscopy provide a unique opportunity for this research. Dr. Bagchi’s profound expertise will be instrumental in guiding the advanced spectroscopic experiments.
Biological membranes are vital to living system functions such as transport, recognition, and signaling. The unique properties of intracellular water, distinct from bulk water, arise from the presence of various macromolecular crowding agents, leading to layers of ordered, osmotically inactive water around cellular components. Small hydrophilic molecules like sugars and osmolytes are also present at high concentrations, playing a key role in stabilizing lipid membrane structures and preserving their functionality under environmental stress. Understanding these interactions at a molecular level is paramount.
The primary aim of this research proposal is to elucidate the influence of different crowding agents on 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) lipid membranes and their interfacial water structure, both in the presence and absence of crowders, utilizing 2D IR and VSS.
Furthermore, recognizing that proteins occupy approximately 30% of the plasma membrane surface, I will investigate the effect the effect of proteins like arrestine, and cytochrome C on specific model lipid membranes. This comprehensive approach will quantify the effects of both crowding agents and proteins on the ultrafast interfacial hydrogen-bond dynamics near biological membranes.