(6et) The Physical Cell: Impact of Mechanics and Rheology on Cellular Function

The internal environment of a living cell comprises a uniquely complex physical milieu for the molecular interactions, conformational changes, and transport processes that underly cell function. My research focuses on examining the basic physical phenomena that underly biological processes at the molecular and cellular level. I develop multiscale models, employing both analytical and computational techniques, that interface directly with experimental data. My work draws on concepts from continuum mechanics, fluid dynamics, and statistical physics to address the interplay of structure, transport, and biological function.

As a doctoral student with Prof. Andrew Spakowitz, I focused on studying how the mechanical properties of DNA impact the packaging and accessibility of the genome. I investigated the role of DNA elasticity in mediating long-range cooperativity between DNA binding proteins, in the packaging of DNA into compact chromatin fibers, and in the fluctuation-dependent kinetics of enzymes that access the DNA. My work on the statistics of large DNA-protein complexes spurred the development of a generalized approach for coarse-grained modeling of polymer systems by mapping onto effective elastic chains. This methodology enables simulations of polymer dynamics and statistics on much larger length scales than were previously accessible.

As a postdoctoral scholar with Prof. Julie Theriot, I study the rheology, fluctuations, and mechanics of the cytoplasm in motile cells. I focus on white blood cells (neutrophils), which exhibit rapid motion accompanied by morphological dynamics. I have developed a novel analysis method for passive microrheology studies in a flowing complex fluid, applying this technique to demonstrate that the neutrophil cytoplasm behaves as a viscous fluid. I also investigate the general physical problem of mixing and dispersion in an actively fluctuating membrane-enclosed fluid domain, elucidating the role of whole-cell deformation on the internal motion of intracellular components. This collaborative work combines analytical and computational studies with direct measurement of cell shape dynamics and organelle motion within living cells at high temporal and spatial resolution.

My future work will focus on the collective physical phenomena that underly transport, mechanics, and kinetics on a cellular scale. In particular, I will explore the impact of cytoplasmic fluctuations and spatial heterogeneity on biomolecular transport and interactions within the cell, as well as the emergence of cell mechanical properties from the dynamic cytoskeletal polymer network. I intend to leverage my background in multiscale biophysical modeling to forge novel links between molecular-scale mechanics and large-scale whole-cell phenomena.