The actin cytoskeleton drives many essential biological processes, from cell morphogenesis to motility. Assembly of functional actin networks requires control over the speed at which actin filaments grow. How this can be achieved at the high and variable levels of soluble actin subunits found in cells is unclear. Here we reconstitute assembly of mammalian, non-muscle actin filaments from physiological concentrations of profilin-actin. We discover that under these conditions, filament growth is limited by profilin dissociating from the filament end and the speed of elongation becomes insensitive to the concentration of soluble subunits. Profilin release can be directly promoted by formin actin polymerases even at saturating profilin-actin concentrations. We demonstrate that mammalian cells indeed operate at the limit to actin filament growth imposed by profilin and formins. Our results reveal how synergy between profilin and formins generates robust filament growth rates that are resilient to changes in the soluble subunit concentration.

Regarding the experimental observation that microtubule catastrophe can be described as a multistep process, we extend the Dogterom-Leibler model for dynamic instability in order to discuss the effect that such a multistep catastrophe mechanism has on the distribution of microtubule lengths in the two regimes of bounded and unbounded growth. We show that in the former case, the steady state length distribution is non-exponential and has a lighter tail if multiple steps are required to undergo a catastrophe. If rescue events are possible, we detect a maximum in the distribution, i.e., the microtubule has a most probable length greater than zero. In the regime of unbounded growth, the length distribution converges to a Gaussian distribution whose variance decreases with the number of catastrophe steps. We extend our work by applying the multistep catastrophe model to microtubules that grow against an opposing force and to microtubules that are confined between two rigid walls. We determine critical forces below which the microtubule is in the bounded regime, and show that the multistep characteristics of the length distribution are largely lost if the growth of a microtubule in the unbounded regime is restricted by a rigid wall. All results are verified by stochastic simulations.

Regarding the experimental observation that microtubule catastrophe can be described as a multistep process, we extend the Dogterom--Leibler model for dynamic instability in order to discuss the effect that such a multistep catastrophe mechanism has on the distribution of microtubule lengths in the two regimes of bounded and unbounded growth. We show that in the former case, the steady state length distribution is non-exponential and has a lighter tail if multiple steps are required to undergo a catastrophe. If rescue events are possible, we detect a maximum in the distribution, i.e., the microtubule has a most probable length greater than zero. In the regime of unbounded growth, the length distribution converges to a Gaussian distribution whose variance decreases with the number of catastrophe steps. We extend our work by applying the multistep catastrophe model to microtubules that grow against an opposing force and to microtubules that are confined between two rigid walls. We determine critical forces below which the microtubule is in the bounded regime, and show that the multistep characteristics of the length distribution are largely lost if the growth of a microtubule in the unbounded regime is restricted by a rigid wall. All results are verified by stochastic simulations.

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