Biology

Dr. Ramakrishnan Natesan
Department of Bioengineering, University of Pennsylvania

Emerging experimental evidences are pointing to the role of the cell membrane as a signalosome, i.e., a unit that governs cell function through soft signals originating from subtle/drastic modulations in the membrane curvature. In this context, understanding the various mechanisms that regulate cell membrane curvature is essential to build models to understand mechanotransduction. In this talk, I will present a multiscale theoretical/computational perspective, using three specific problems, to demonstrate how membrane curvature is induced at multiple length scales and what are its implications on the process of specific adhesion?

I will first present an in silico tether pulling technique to estimate the excess area in cell membranes that are stored in the form of thermal undulations. I will demonstrate the quantitative validity of the model and also show how the various computationally predicted scaling laws may be used alongside experiments to mechanotype cells. In the second part, I will present a multiscale computational framework to quantify membrane-protein interactions, which in turn enables us to use molecular scale information to construct the thermodynamics of the system. I will demonstrate how various free energy techniques may be used to predict morphological transitions in cell membranes, and show that membrane tubulation at the mesoscale proceeds via a micellization like process. Having shown how curvature manifests at various length scales, I will next present how a nanosized particle, such as a functionalized nanocarrier or a virus, adheres to a cell surface
through multivalent specific receptor-ligand interactions. I will primarily focus on the role of the cellular mechanotype and the various configurational entropies in determining the binding affinity of the particle.