A generalized Flory-Stockmayer kinetic theory of connectivity percolation and rigidity percolation of cytoskeletal networks

Author summaryThe actin cytoskeleton is a complex dynamic system, regulated by multiple proteins that bind to actin filaments. Some actin-binding proteins are crosslinkers, which can bind pairs of actin filaments, forming actin networks. Actin crosslinkers can be passive linkers, providing only structural integrity, or can be active linkers such as myosin motors, which exert forces on the network. Experiments have shown that crosslinked actin networks can behave viscously when the number of passive crosslinkers is low, but become elastic, when there are many crosslinkers. Motors can only lead to contraction of the network when there is an intermediate concentration of passive crosslinkers. The behavior of networks in the cell depends on the concentration and activity of several distinct crosslinkers, which have different binding sites, geometries, affinities, and concentrations. In this work we propose a simple analytical model based on chemical kinetics and the Flory-Stockmayer theory that gives us insight into how different crosslinkers interact with the actin filaments so as to give rise to the emergent mechanical behavior. This theory also allows us to compute analytically several crucial aspects of the development of the mechanical properties during network assembly. Actin networks are essential for living cells to move, reproduce, and sense their environments. The dynamic and rheological behavior of actin networks is modulated by actin-binding proteins such as alpha-actinin, Arp2/3, and myosin. There is experimental evidence that actin-binding proteins modulate the cooperation of myosin motors by connecting the actin network. In this work, we present an analytical mean field model, using the Flory-Stockmayer theory of gelation, to understand how different actin-binding proteins change the connectivity of the actin filaments as the networks are formed. We follow the kinetics of the networks and estimate the concentrations of actin-binding proteins that are needed to reach connectivity percolation as well as to reach rigidity percolation. We find that Arp2/3 increases the actomyosin connectivity in the network in a non-monotonic way. We also describe how changing the connectivity of actomyosin networks modulates the ability of motors to exert forces, leading to three possible phases of the networks with distinctive dynamical characteristics: a sol phase, a gel phase, and an active phase. Thus, changes in the concentration and activity of actin-binding proteins in cells lead to a phase transition of the actin network, allowing the cells to perform active contraction and change their rheological properties.

Automated summary

The actin cytoskeleton, modulated by actin-binding proteins, is essential for cell movement, reproduction, and sensing of the environment. This study proposes a simple analytical model based on chemical kinetics and the Flory-Stockmayer theory to understand how different actin-binding proteins interact with actin filaments to give rise to emergent mechanical behavior. It is found that changes in the concentration and activity of actin-binding proteins can lead to a phase transition of the actin network, allowing cells to perform active contraction and change their rheological properties.