Interplay of active processes modulates tension and drives phase transition in self-renewing, motor-driven cytoskeletal networks

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.

Morphological Transformation and Force Generation of Active Cytoskeletal Networks

“…We employed our previous coarse-grained Brownian dynamics model for actomyosin structures [13]. In the model, actin filaments, actin cross-linking proteins (ACPs), and motors are simplified into interconnected cylindrical segments (Fig 1A).…”

“…In our previous study, we demonstrated that actin turnover modulates the buildup and sustainability of tension generated by actomyosin networks [13]. We tested effects of actin turnover on bundle formation and tension generation by imposing actin treadmilling at various rates ( k t,A ) under a condition where bundles generate unsustainable tension and eventually form aggregates in the absence of any turnover ( R M = 0.08 and R ACP = 0.01).…”

“…We found that during the transition from a network into a bundle, actin filaments undergo buckling and reorientation in various ways, and a large portion of tension is built during the structural reorganization rather than after bundle formation. In addition, we incorporated systematic variations of initial filament orientation that have not been included in our previous studies [13, 16, 24–27], motivated by observation that transverse arcs located at the interface between lamellipodia and lamella are formed by compaction and realignment of actin filaments with biased orientations within the lamellipodia [28]. …”

“…We repeat this calculation on 10 cross-sections and compute the average. Sustainability of the tension is calculated in the same manner as in [13]. …”

Molecular simulations of cellular processes

“…Simulating macromolecule stability and interactions in a eukaryotic-like cell requires a large effort for the presence of localized and pervasive structures (Neri et al 2013;Smith et al 2014;Unterberger and Holzapfel 2014;Mak et al 2015Mak et al , 2016Gao et al 2015;Nguyen et al 2016;Popov et al 2016;Reddy and Sansom 2016;Chavent et al 2016;Foffano et al 2016;Niesen et al 2017;Tachikawa and Mochizuki 2017). Future investigations will be devoted to simulating dynamical processes involving the cytoskeleton and the membranes, such as the trafficking of macromolecules and vesicles to their sub-cellular localization (Miller et al 2016).…”