Architecture and Connectivity Govern Actin Network Contractility

Abstract

SUMMARY Actomyosin contractility plays a central role in a wide range of cellular processes, including the establishment of cell polarity, cell migration, tissue integrity, and morphogenesis during development. The contractile response is variable and depends on actomyosin network architecture and biochemical composition. To determine how this coupling regulates actomyosin-driven contraction, we used a micropatterning method that enables the spatial control of actin assembly. We generated a variety of actin templates and measured how defined actin structures respond to myosin-induced forces. We found that the same actin filament crosslinkers either enhance or inhibit the contractility of a network, depending on the organization of actin within the network. Numerical simulations unified the roles of actin filament branching and crosslinking during actomyosin contraction. Specifically, we introduce the concept of “network connectivity” and show that the contractions of distinct actin architectures are described by the same master curve when considering their degree of connectivity. This makes it possible to predict the dynamic response of defined actin structures to transient changes in connectivity. We propose that, depending on the connectivity and the architecture, network contraction is dominated by either sarcomeric-like or buckling mechanisms. More generally, this study reveals how actin network contractility depends on its architecture under a defined set of biochemical conditions.

Geometry and network connectivity govern the mechanics of stress fibers

“…Precisely how SF network heterogeneities arise and evolve represents an important open question, and it is possible that this may be a function of the cell's adhesive and spreading history. Indeed, our findings complement the recent, elegant demonstration that patterning reconstituted actomyosin network architecture can modulate contractility (34). Development of analogous micropatterning strategies for living cells may make it possible to test the hypotheses raised in our study by engineering the details of the internal SF network through strategic placement of adhesions.…”

Actin Rings of Power

“…Yet the basic principles underlying the relationship between actin ring organization and function have only begun to be unraveled, due to technical limitations of visualizing the actin network organization within rings (e.g., by electron or super-resolution fluorescence microscopy). In a recent study, the role of actin network organization and connectivity for actomyosin ring contraction was analyzed (Ennomani et al, 2016). As expected, it was found that in the absence of actin cross-linkers, ordered anti-parallel (sarcomere-like) bundles showed a higher level of contractility than disordered actin networks or actin bundles with mixed polarity.…”

Cytoskeletal control of B cell responses to antigens

“…If myosin slides actin filaments that are structurally incompatible with contraction, the filaments buckle and break 26 . Therefore, myosin not only contracts, but also remodels the cortex 27,28 . In addition, myosin can induce flows of free actin filaments into aster-like formations 29,30 , and potentially transport proteins via co-assembly with the cargo-binding protein MYO18A 31 .…”