Nucleation causes an actin network to fragment into multiple high-density domains

Computational simulations reveal that Abl activity controls cohesiveness of actin networks in growth cones

“…Rather, both the simulations here and the quantitative analyses in our previous work ( Clarke et al. , 2020a , b ; Chandrasekaran et al. , 2022 ) suggest that the WT condition encompasses substantial stochastic fluctuations that populate a range of actomyosin network architectures.…”

“…This is consistent with the complex and highly variable collection of peaks observed in the 1D simulation profiles at high Arp2/3. In the next section, we establish that the patterns in order parameters measured at high Arp2/3 concentrations along the cylinder axis, such as actin spread and pair correlation function, are mechanistically a consequence of actin fragmentation ( Chandrasekaran et al ., 2022 ). Thus, changing Arp2/3 concentration has a profound effect on the internal organization of the actin network, with low Arp2/3 promoting consolidation of actin in a homogeneous mass and increasing Arp2/3 spreading actin into multiple masses.…”

“…At the actin level, we see that at low [Arp2/3], most of the actin is present in long filaments, and it shifts steadily toward short filaments at high [Arp2/3] (Supplemental Figure S6). We discuss this phenomenon in more detail in work presented elsewhere ( Chandrasekaran et al ., 2022 ). In brief, at low [Arp2/3], most of the actin is present in filaments extended from the original seeds (Supplemental Figure S6).…”

“…Reduced effectiveness of contractility in this condition is also apparent as local actin concentration exceeds bulk only in small patches of the distribution. (The role of myosin in this evolution is studied in detail elsewhere ( Chandrasekaran, et al ., 2022 .) In contrast to varying Arp2/3, increasing Ena at low Arp2/3 concentrations modestly broadens the width of a central peak in the actin distribution, while at higher Arp2/3, increasing Ena has little discernible effect.…”

A new view of axon growth and guidance grounded in the stochastic dynamics of actin networks

“…The ‘growth cone’ was then allowed to undergo dynamics for 2000 s (long enough to achieve steady state), incorporating both chemical events, such as polymerization, branching, bundling and contractility, as well as relaxation of physical strain every 25 ms. Kinetic constants for the simulations were taken from published values for the relevant dynamic processes, and concentration ranges of components were selected based on a combination of theoretical considerations and empirical tests [ 52 , 94 ]. While extraordinarily rich in detail, the resulting findings were remarkably simple in terms of the principles that they revealed.…”