(6fa) Design of Biomimetic Functional Nanomaterials to Study Integral Membrane Proteins

Authors: 
Vaish, A., University of Delaware

Integral membrane proteins (IMPs) reside within the cellular membrane and play a key role in modulating a wide range of physiological processes, from neuronal signaling to immune and hormonal response. Their malfunctioning has been implicated in various diseases, including cancer and cardiovascular diseases, which makes them an important pharmaceutical target. The native lipidic environment is imperative for the stability and activity of IMPs, which makes in vitro studies of these proteins very challenging. The overarching goal of my research has been to develop novel biomimetic interfaces for reconstituting IMPs to facilitate their structural and functional studies. For example, during my postdoctoral research at the NIST Center for Neutron Research, I fabricated a functionalized nanotubular membrane for reconstituting IMPs, and used this platform in combination with neutron scattering techniques to determine the IMP’s structure. Additionally, during my graduate research, I developed a microarray-based platform to selectively immobilize IMPs for high-throughput target screening. Currently, my research at the University of Delaware is focused on studying the role of surfactant micelles in the stabilization and crystallization of IMPs. Surfactant micelles are widely used as a bilayer mimic for reconstituting IMPs in protein-detergent complexes (PDCs). We are employing nuclear magnetic resonance and small-angle neutron and x-ray scattering (SANS and SAXS) techniques to study the stability of PDCs over molecular and microscopic length scales, respectively, which we expect will enable the rational design of PDCs and IMP crystallization trials. Using my interdisciplinary research background in biomaterials, nanotechnology, neutron scattering techniques, and IMPs, I intend to develop an independent research program on biomimetic functional nanomaterials for: biophysical characterization of IMPs using neutron scattering; biosensors to monitor IMPs; and high-throughput drug screening platforms.