Understanding How Cofilin Breaks an Actin Polymer at the Molecular and Cellular Levels

Identifying how the chemical and mechanical properties of biopolymers are coupled at the molecular level is central to understand the regulation of cellular organization and processes. The assembly of protein actin into biopolymers and networks powers many eukaryotic cell movements and provides cells with mechanical strength and integrity. Cofilin is the essential actin regulatory protein that plays a critical role in promoting actin assembly and disassembly dynamics by fragmenting filaments. Although cofilin effects on actin dynamics have been extensively studied, the molecular mechanism of cofilin-mediated filament fragmentation is not understood. In this talk, I will present how actin filament mechanics and structure are regulated by cofilin at the molecular and cellular levels through comprehensive molecular/cellular biophysical approaches. My work reveals that the cofilin-mediated severing of actin filament is mainly driven by the dissociation of a single, site-specific “stiffness cation” that alters filament structure and mechanical properties. I evaluate the proposed mechanism with site-specific actin mutants, and provide a structural and mechanical basis for filament fragmentation. Moreover, I show that actin filament severing is the essential function of cofilin in cells. This study suggests that discrete salt interactions serve a central regulatory function in mediating actin polymer fragmentation and dynamics, and further establishes how cation-mediated perturbations may play roles in the mechanical stability of non-covalent biopolymers and assemblies. Finally, I will discuss the outlook of my future research program focusing on the molecular “mechanosensing” mechanisms of cytoskeletal biopolymers in vitro and in cells.

Bio:

Dr. Hyeran Kang is currently a postdoctoral research associate in the Department of Molecular Biophysics & Biochemistry at Yale University. She received her B.S. and M.S. from Seoul National University, Korea, in physics (condensed matter physics for MS degree) in 1999 and 2001, respectively. She earned a Ph.D. from Brown University in physics (biophysics) in 2010. From 2007 to 2008, she worked as a visiting scholar in the Institute of Medicine and Engineering at the University of Pennsylvania. Her research focuses on the mechanics of biopolymers and networks, with an emphasis on the molecular mechanisms of actin filament assembly dynamics and mechanics. In this endeavor, she develops and integrates molecular and cellular biophysics with pure protein biochemistry as well as bioengineering techniques.