Nanomechanical studies of cells and biomolecules

Abstract The research in our laboratory is centered on the development of force-based mechanical approaches to biomolecular and cellular imaging, and leveraging these capabilities to study a number of questions in biomolecular dynamics and cells mechanics. Our approach to imaging offers new capabilities in probing chemical, mechanical and electrical characteristics of biological systems from molecules to cells. In biomolecular imaging, we focus on problems in structural biology that can benefit from direct imaging in physiologically relevant conditions where mechanical approaches like atomic force microscopy (AFM) have advantages. We currently develop an AFM-based method to image dynamics of RNA/protein complexes and membrane proteins with Angstrom scale resolution. In cell mechanical studies, we recently developed a cell stiffness imaging method that provided unprecedented spatial resolution, which helped reveal nanoscale patterns in cell stiffness that are described by precise mathematical relationships. Existence of these patterns are not predicted by the current quantitative models of cell mechanics. We developed a new model that not only explained our findings, but also made new testable predictions that we subsequently confirmed. These molecular and cellular studies shape the current research goals in our laboratory. On the biomolecular imaging front, our goal for the next five years is to develop our technology to achieve imaging of biomolecular dynamics in physiologically relevant conditions with Angstrom- scale resolution. Currently, such high-resolution data is mainly coming from methods that work with frozen or crystallized samples, which prevent observations of biomolecular dynamics. On the cell mechanics front, our goals for the next five years include further developing our cell mechanical model to address a large discrepancy between results measured by different methods used by researchers. We believe the discrepancy is not due to technical problems of various methods, but rater due to underlying assumptions about contact mechanics of cells, that is, a conceptual issue. Addressing this discrepancy can help better predict cell mechanical behavior in physiological contexts. We are also interested in investigating electromechanical coupling in cell membranes and have already built a uniquely suited experimental setup to probe electromechanical coupling in cell membranes. We are motivated by our recent observations of strong coupling effects and potential effects of coupling on gating of ion channels and the morphology of membranous organelles. Overall, the vision of our research program is set by the important roles of nanoscale mechanical interactions in biology, and we develop biophysical models and experimental capabilities to realize our vision.