  Cellular actin dynamics result from collective action of hundreds of
regulatory proteins, majority of which target actin filaments at their barbed
ends. Three key actin binding proteins - profilin, cofilin and twinfilin
individually depolymerize filament barbed ends. Notwithstanding recent leaps in
our understanding of their individual action, how they collectively regulate
filament dynamics remains an open question. In absence of direct and
simultaneous visualization of these proteins at barbed ends, gaining
mechanistic insights has been challenging. We have here investigated
multicomponent dynamics of profilin, cofilin and twinfilin using a hybrid
approach that combines high throughput single filament experiments with theory.
We discovered that while twinfilin competes with profilin, it promotes binding
of cofilin to filament sides. Interestingly, contrary to previous expectations,
we found that profilin and cofilin can simultaneously bind the same filament
barbed end resulting in its accelerated depolymerization. Our study reveals
that pair-wise interactions can effectively capture depolymerization dynamics
in simultaneous presence of all three proteins. We thus believe that our
approach of employing a theory-experiment dialog can potentially help decipher
multicomponent regulation of actin dynamics.
