A major challenge in cell and organism biology is to understand how living cell physiology
emerges from the biophysical properties of individual macromolecules. The morphological and
physical behaviors of cells required for cell adhesion, migration and division depend on the proper
spatial and temporal regulation of a vast hierarchy of multi-protein machines, called the cytoskeleton.
However, while we are gaining increasing amounts of knowledge of properties of individual
cytoskeletal proteins, we have very little knowledge about the self-assembly and physical properties of
multi-protein assemblies that form physical structures to transmit mechanical information up to cellular
length scales. For example, we do not understand how forces generated by individual molecular
motors are exploited by cytoskeletal assemblies to regulate morphogenesis and force generation at
the cellular level. Current understanding of the physical behavior of the cellular cytoskeleton has
been limited both by the lack of experimental techniques to probe the dynamic structure and physical
properties of mesoscopic cytoskeletal assemblies in living cells. I propose to establish the
experimental tools to study the biophysical properties of cytoskeletal matter in living cells by
integrating approaches from condensed matter physics with molecular cell biology. This work will
identify the underlying physics of emergent cytoskeletal assemblies and will provide predictive
analytical models to link our understanding of the biophysics of molecules to cell behaviors. Finally,
this work will impact the treatment of diseases that are a result of misregulation of the physical
behaviors of cells, including cancer metastasis and cardiac diseases. |