Abstract
The actin cytoskeleton—a complex, nonequilibrium network consisting of filaments, actin-crosslinking proteins (ACPs) and motors—confers cell structure and functionality, from migration to morphogenesis. While the core components are recognized, much less is understood about the behaviour of the integrated, disordered and internally active system with interdependent mechano-chemical component properties. Here we use a Brownian dynamics model that incorporates key and realistic features—specifically actin turnover, ACP (un)binding and motor walking—to reveal the nature and underlying regulatory mechanisms of overarching cytoskeletal states. We generate multi-dimensional maps that show the ratio in activity of these microscopic elements determines diverse global stress profiles and the induction of nonequilibrium morphological phase transition from homogeneous to aggregated networks. In particular, actin turnover dynamics plays a prominent role in tuning stress levels and stabilizing homogeneous morphologies in crosslinked, motor-driven networks. The consequence is versatile functionality, from dynamic steady-state prestress to large, pulsed constrictions.
Highlights
The actin cytoskeleton—a complex, nonequilibrium network consisting of filaments, actin-crosslinking proteins (ACPs) and motors—confers cell structure and functionality, from migration to morphogenesis
We explore the direct connections between biochemical kinetics and mechanics at the cytoskeletal component level and simulate the resulting global cytoskeletal network
We use a three-dimensional (3D) Brownian dynamics computational model of the active actin cytoskeleton, incorporating core microscopic components and functionality— actin filaments thatpolymerize, ACPs that bind and unbind in a force-dependent manner, and myosin II motors that walk and generate tension along actin filaments. These components are mechanical in nature, with bending and extensional stiffnesses, enabling mechanics and kinetics to be concurrently simulated from the component to network scales
Summary
The actin cytoskeleton—a complex, nonequilibrium network consisting of filaments, actin-crosslinking proteins (ACPs) and motors—confers cell structure and functionality, from migration to morphogenesis. Hannezo et al.[34] developed a mathematical model that considers actin turnover and diffusion and determined a phase diagram of cytoskeletal states, including homogeneous states, stationary spatial patterns of actin that mimicked periodically spaced supracellular actin rings in the Drosophila tracheal tubule, and chaotic patterns that vary in time due to nonlinearity in actin turnover While these models are relatively simple and general, it is unclear how different abstract components and coarsened terms of constitutive equations relate to mechano-chemical kinetics and turnover mechanisms and dynamics of realistic cytoskeletal features, such as motor walking, actin treadmilling and ACP unbinding, which interact in large numbers. We experimentally probe the cytoskeletal dynamics of live cells under disrupted actin polymerization, and we capture the time scales of morphological phase transition
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