388324 The Physical Cell: Impact of Mechanics and Rheology on Cellular Function
The internal microenvironment of a living cell comprises an intricate choreography of molecules that must be transported from one location to another, elastic forces that must be overcome or harnessed into useful work, and interdependent chemical reactions whose rates must be carefully controlled. 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 demonstrated that the elasticity of the DNA molecule can give rise to tension-mediated cooperative binding between DNA-bending proteins, allowing them to interact across a wide range of length scales without direct protein-protein contact. I also investigated the role of this elasticity in the packing of DNA into compact chromatin fibers, and the connection between packaging fluctuations and force-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 was previously possible.
As a postdoctoral scholar with Prof. Julie Theriot, I investigate cytoplasmic mechanics in motile neutrophils. These cells exhibit rapid motion accompanied by dynamic changes in shape that arise from large-scale fluctuations at the cell boundary, driven by active polymerization processes. Using a combination of analytical theory and simulations, I study the motion of particles near an actively fluctuating membrane. I apply this model directly to cytoplasmic dynamics in motile cells by treating the cell interior as a viscous fluid driven by boundary fluctuations that are tracked using phase microscopy. Fluorescent tracking of intracellular particles indicates that their relative motion is consistent with the predictions of this simple model. In particular, I demonstrate that fluid flows arising from the cell shape dynamics can contribute significantly to mixing and transport of large complexes and organelles within the cell.
My future research goals center on studying the physical processes underlying the propagation of chemical and mechanical signals within a cell. I intend to use my background in multiscale biophysical modeling as a springboard for addressing fundamental problems of how transport phenomena, active mechanical fluctuations, and intracellular spatial organization impact the structure and kinetics of biomolecular networks. Hijacking cellular machinery to engineer novel circuits or to induce therapeutic effects necessitates an ability to harness the kinetic properties of these reaction networks. The role of cytoplasmic rheology and mechanics in modulating biomolecular processes within the cell thus presents a rich set of questions of direct relevance to cellular engineering.