Metal-Induced Energy Transfer based Electrometry and Nanometry: Dissecting Electrostatic Phenomena in Biological Processes

ongoing

Almost all biological processes, involving molecular trafficking, signal-transduction, cell-to-cell interactions, hinge on precisely orchestrated electrostatic interactions, arising from electrical charges on biomolecules and membranes. Yet, our understanding of the role of electrostatics in these fundamental processes remains elusive due to the absence of quantitative methods to measure the electrical charges of biomolecules and to map the surface charge distribution of membranes. This challenge is further compounded by the requirement of capturing molecular and membrane dynamics that take place at the nanometre length scales and nano- to sub-millisecond time scales. The overall objective of this project is to bridge this technological gap by introducing Metal-Induced Energy Transfer based Electrometry and Nanometry (MIETEN), a groundbreaking technology that will quantify the electrical charge of biomolecules or membranes while capturing their dynamics with nanometre spatial and microsecond temporal resolutions. We will demonstrate MIETEN for measuring: (i) the charges and sizes of individual membrane proteins, (ii) membrane protein structural changes, conformational dynamics, and spatial organization in response to changes in membrane potential, (iii) reaction-diffusion kinetics at a charged membrane, (iv) mechanical properties and dynamics of membranes containing charged inclusions and (v) interactions between two charged membranes. The ability to measure biomolecular and membrane electrical charges and to elucidate the role of electrostatics in structure, organization, and interactions of proteins, as well as in membrane dynamics and intermembrane interactions, will be crucial for our understanding of fundamental biology and for advancing biomedical research. MIETEN will open new frontiers in studying protein and membrane dynamics and impact drug development, early diagnostics, and therapeutic interventions.