Executive Summary : | The project's main objective is to develop cell-free biomembrane platforms on nanoparticle surfaces using phospholipids, transmembrane proteins, and receptors to maintain a native lipid-protein ratio for biophysical studies and screening applications. This research proposal is based on designing nanoparticle-supported native stable biomembranes to investigate the binding, penetration, and association of membrane-targeting viral or bacterial pathogens using spectroscopic and analytical tools. The understanding of biomembrane formation strategies on the nanoparticle surfaces and various kinetics parameters of membrane-pathogen interactions will bring an interdisciplinary perspective to investigate membrane-associated processes in the field of biosensor development. Transmembrane proteins and receptors are Nature's biorecognition and inherent components for sensing and signal transduction. It is most challenging to integrate these biomolecules in their native environments. Artificial vesicles or planar-supported lipid bilayers (sLBs) are exclusively used to fabricate protein-functionalized membranes for biotechnological applications. Vesicles are suitable for capturing the role of membrane curvature and deformation in membrane-associated biophysical processes; however, they have limited stability in complex environments. Planar sLBs are significantly stable compared to the vesicles due to underlying support but cannot capture the effect of membrane curvature or deformation on biophysical processes. To address these limitations, I am proposing a stable biomembrane that maintains native lipid-protein associations on different nanoparticle surfaces. In this research proposal, the approaches for the formation of native biomembrane using plasma membrane vesicles (cell blebs, exosomes, etc.) will be established on a wide range of nanoparticle surfaces (e.g., silica, gold, iron oxides, and porous) to demonstrate the properties of the biomembranes and nanoparticles in recognition of membrane-pathogen (e.g., Influenza viral proteins, bacterial toxins, etc.) interactions, ion channel properties of transmembrane proteins (e.g., light-driven proton pump bacteriorhodopsin or ATP gated ion channel P2X receptors), etc. These biologically complex robust biomembrane platforms on nanoparticle surfaces will allow dual-mode complementary data collection (fluorescently labeled lipids as a marker and nanoparticle as a sensor interface). These features make nanoparticle-supported biomembrane a technology that can shift how biomembrane can be used for biophysical studies, detection, and screening applications. |