Using theory as a microscope: Modeling multiprotein interactions at the actin filament barbed end
Cells regulate the assembly and remodeling of actin networks with the help of numerous actin-binding proteins, many of which specifically target the barbed ends of actin filaments. Mechanistic insights into these processes have been challenging to obtain due to the difficulty in simultaneously visualizing these proteins directly at barbed ends. Recent work from the Shekhar Lab employed theoretical models as a “microscope” to understand the interactions of three key proteins—profilin, cofilin, and twinfilin—at the actin filament barbed end. The study explored how these proteins, which individually promote actin filament depolymerization, collectively regulate barbed end disassembly. Strikingly, the research revealed that while twinfilin competes with profilin, it also promotes cofilin binding to filament sides. Contrary to previous assumptions, profilin and cofilin can simultaneously bind to the same filament barbed end, resulting in accelerated depolymerization. Furthermore, the findings demonstrate that pairwise interactions between these proteins are sufficient to predict their collective dynamics. This work, led by graduate student Ankita Arya, was conducted in collaboration with Dr. Sandeep Choubey from the Institute of Mathematical Sciences (India) and was recently published in PRX Life: http://journals.aps.org/prxlife/abstract/10.1103/PRXLife.2.033002.