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Branching activity switches actin network between connected and fragmented states in a myosin-dependent manner
(2021) Chandrasekaran, Aravind; Giniger, Edward; Papoian, Garegin
Actin networks rely on nucleation mechanisms to generate new filaments because de-novo nucleation is kinetically disfavored. Branching nucleation of actin filaments by Arp2/3, in particular, is critical for actin self-organization. In this study, we use the simulation platform for active matter, MEDYAN, to generate 2000s long stochastic trajectories of actin networks, under varying Arp2/3 concentrations, in reaction volumes of biologically meaningful size (> 20m3). We find that mechanosensitive dynamics of Arp2/3 increases the abundance of short filaments and increases network treadmilling rate. By analyzing the density-fields of F-actin, we find that at low Arp2/3 concentration, F-actin is organized into a single, connected and contractile domain, while at elevated Arp2/3 levels (10nM and above), such contractile actin domains fragment into smaller domains spanning a wide range of volumes. These fragmented domains are extremely dynamic, continuously merging and splitting, owing to the high treadmilling rate of the underlying actin network. Treating the domain dynamics as a drift-diffusion process, we find that the fragmented state is stochastically favored, and the network state slowly drifts towards the fragmented state with considerable diffusion (variability) in the number of domains. We suggest that tuning the Arp2/3 concentration enables cells to transition from a globally coherent cytoskeleton, whose response involves the entire cytoplasmic network, to a fragmented cytoskeleton where domains can respond independently to local varying signals.
Data for "A tug of war between filament treadmilling and myosin induced contractility generates actin ring"
(2022-06-23) Ni, Qin; Wagh, Kaustubh; Pathni, Aashli; Ni, Haoran; Vashisht, Vishavdeep; Upadhyaya, Arpita; Papoian, Garegin A.; Upadhyaya, Arpita; Papoian, Garegin A.
In most eukaryotic cells, actin filaments assemble into a shell-like actin cortex under the plasma membrane, controlling cellular morphology, mechanics, and signaling. The actin cortex is highly polymorphic, adopting diverse forms such as the ring-like structures found in podosomes, axonal rings, and immune synapses. The biophysical principles that underlie the formation of actin rings and cortices remain unknown. Using a molecular simulation platform, called MEDYAN, we discovered that varying the filament treadmilling rate and myosin concentration induces a finite size phase transition in actomyosin network structures. We found that actomyosin networks condense into clusters at low treadmilling rates or high myosin concentration but form ring-like or cortex-like structures at high treadmilling rates and low myosin concentration. This mechanism is supported by our corroborating experiments on live T cells, which exhibit ring-like actin networks upon activation by stimulatory antibody. Upon disruption of filament treadmilling or enhancement of myosin activity, the pre-existing actin rings are disrupted into actin clusters or collapse towards the network center respectively. Our analyses suggest that the ring-like actin structure is a preferred state of low mechanical energy, which is, importantly, only reachable at sufficiently high treadmilling rates.