Profilin-regulated actin polymerization dynamics at high monomer concentrations

Abstract Actin polymerization in the cytoskeleton drives crucial dynamical biological processes such as cell motility and morphogenesis. Recent experiments 1 show that binding to profilin plays a crucial role in controlling the maximal polymerization speed of F-actin at cellular actin concentrations. These experiments are successfully described by a four reaction kinetic model, which predicts a Michaelis-Menten-like saturation of growth speed at high profilin-actin concentrations. In this work, we further analyze the four reaction model in terms of master equations and using the concept of two polymerization cycles, a pure actin cycle and a profilin-actin cycle and propose further experimental setups to gain access to all kinetic rates of the model. We find that varying the profilin excess leads to a profilin-dependent Michaelis constant for the growth speed. For polymerization against an external force, we identify a unique stall force as an indicator of energetically balanced profilin-driven polymerization, i.e., for the absence of coupling to other chemical processes providing energy input. Calculating length diffusivity (or Fano factor) we show that actin growth becomes much more precise by profilin-regulation and almost reaches precision bounds set by thermodynamic uncertainty relations.