THEORETICAL APPROACHES IN CELL BIOLOGY
PHYSICS OF ACTIVE, EVOLVING SYSTEMS

Since the cell surface has to manage and process a large spectrum of information from the outside into the interior of the cell, its composition must be organized and regulated over different spatial and temporal scales. A great challenge in cell biology is to understand  the physico-chemical principles that govern this regulatable organization. Together with Satyajit Mayor's group, we have been studying the organization of molecules, such as lipids and proteins, on the cell surface and how they engage in processes such as endocytosis and signaling. Our work suggests a new model for the cell surface, which we call the active composite cell surface, wherein molecules at the cell surface are clustered, localized and transported by cortical actomyosin activity. The spatial distribution and dynamics of these molecules, as measured by a variety of fluorescence methods, can be entirely understood within our active hydrodynamics framework as applied to an active composite cell surface. This framework provides a deeper understanding of the spatiotemporal regulation of chemical reactions in the cell surface, such as those encountered in signaling and sorting.

The remodeling and transport of organelles and vesicles are also active processes. We are interested in the active dynamics of intracellular trafficking in the endosomal and secretory pathaways, which involves the interplay between organelle (membrane) shape, composition and activity of fission, fusion and transport. In this context, we are studying the remodeling dynamics of mitochondria, and the morphogenesis of the Golgi cisternae.

These principles can be carried over to the study of the 3 dimensional organization and dynamics of chromatin embedded in the active nucleoplasm. Together with GV Shivashankar's group we are studying how mechanical stresses propagate into the nucleus to affect chromatin organization and gene expression. We are also studying the microrheology of the nucleus and the effect of active stress fluctuations on the nuclear size and shape and the spatial patterning of local chromatin compaction.