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bioRxiv · 10.1101/2021.11.07.467615

Emergence and maintenance of different sized actin filaments in a common pool of building blocks

Banerjee, D. S.·Banerjee, S.
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Abstract

Actin is one of the key structural components of the eukaryotic cytoskeleton that regulates cellular architecture and mechanical properties. Dynamic regulation of actin filament length and organization is essential for the control of many physiological processes including cell adhesion, motility and division. While previous studies have mostly focused on the mechanisms controlling the mean length of individual actin filaments, it remains poorly understood how distinct actin filament populations in cells maintain different lengths using the same set of molecular building blocks. Here we develop a theoretical model for the length regulation of multiple actin filaments by nucleation and growth rate modulation by actin binding proteins in a limiting pool of monomers. We first show that spontaneous nucleation of actin filaments naturally leads to heterogeneities in filament length distribution. We then investigate the effects of filament growth inhibition by capping proteins and growth promotion by formin proteins on filament length distribution. We find that filament length heterogeneity can be increased by growth inhibition, whereas growth promoters do not significantly affect length heterogeneity. Interestingly, a competition between filament growth inhibitors and growth promoters can give rise to bimodal filament length distribution as well as a highly heterogeneous length distribution with large statistical dispersion. We quantitatively predict how heterogeneity in actin filament length can be modulated by tuning F-actin nucleation and growth rates in order to create distinct filament subpopulations with different lengths. SIGNIFICANCEActin filaments organize into different functional network architectures within eukaryotic cells. To maintain distinct actin network architectures, it is essential to regulate the lengths of actin filaments. While the mechanisms controlling the lengths of individual actin filaments have been extensively studied, the regulation of length heterogeneity in actin filament populations is not well understood. Here we show that the modulation of actin filament growth and nucleation rates by actin binding proteins can regulate actin length distribution and create distinct sub-populations with different lengths. In particular, by tuning concentrations of formin, profilin and capping proteins, various aspects of actin filament length distribution can be controlled. Insights gained from our results may have significant implications for the regulation of actin filament length heterogeneity and architecture within a cell.

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Banerjee, D. S., Banerjee, S.. 2021-11-07. Emergence and maintenance of different sized actin filaments in a common pool of building blocks. https://doi.org/10.1101/2021.11.07.467615

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