Requirements for contractility in disordered cytoskeletal bundles

James Franck Institute, University of Chicago, Chicago, IL 60637, USA.
New Journal of Physics (Impact Factor: 3.56). 03/2012; 14(3). DOI: 10.1088/1367-2630/14/3/033037
Source: PubMed


Actomyosin contractility is essential for biological force generation, and is well understood in highly organized structures such as striated muscle. Additionally, actomyosin bundles devoid of this organization are known to contract both in vivo and in vitro, which cannot be described by standard muscle models. To narrow down the search for possible contraction mechanisms in these systems, we investigate their microscopic symmetries. We show that contractile behavior requires non-identical motors that generate large-enough forces to probe the nonlinear elastic behavior of F-actin. This suggests a role for filament buckling in the contraction of these bundles, consistent with recent experimental results on reconstituted actomyosin bundles.

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    • "As a result, cytoskeletal networks can release elastic stresses stored in the network and undergo large-scale flows. Significant progress has been achieved trough in vitro studies and theoretical analysis of actomyosin networks to understand stress generation in networks with permanent filaments and fixed or unbinding crosslinkers [5] [6] [7] [8] [9] [10] [11]. It is unclear however what is the role of turnover in stress generation and how filament networks can simultaneously rearrange and exert a permanent internal active stress. "
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    ABSTRACT: We study the effect of turnover of cross linkers, motors and filaments on the generation of a contractile stress in a network of filaments connected by passive crosslinkers and subjected to the forces exerted by molecular motors. We perform numerical simulations where filaments are treated as rigid rods and molecular motors move fast compared to the timescale of exchange of crosslinkers. We show that molecular motors create a contractile stress above a critical number of crosslinkers. When passive crosslinkers are allowed to turn over, the stress exerted by the network vanishes, due to the formation of clusters. When both filaments and passive crosslinkers turn over, clustering is prevented and the network reaches a dynamic contractile steady-state. A maximum stress is reached for an optimum ratio of the filament and crosslinker turnover rates.
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    • "This result is quite general, as it requires only a minimal form of disorder, namely polarity-reversal symmetry (i.e., the property that any arrangement of filaments is just as likely as its polarity-reversed counterpart). This is a variant of a more powerful argument valid for onedimensional bundles [12]; a more formal presentation is given in the Supporting Information. Interestingly, this polarity-reversal symmetry can be broken not only through sarcomeric organization, which yields contractility , but also in solution through a dynamical process of motor-filament coalescence and sliding, which favors extension [21]. "
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    ABSTRACT: Movement within eukaryotic cells largely originates from localized forces exerted by myosin motors on scaffolds of actin filaments. Although individual motors locally exert both contractile and extensile forces, large actomyosin structures at the cellular scale are overwhelmingly contractile, suggesting that the scaffold serves to favor contraction over extension. While this mechanism is well understood in highly organized striated muscle, its origin in disordered networks such as the cell cortex is unknown. Here we develop a mathematical model of the actin scaffold's local two- or three-dimensional mechanics and identify four competing contraction mechanisms. We predict that one mechanism dominates, whereby local deformations of the actin break the balance between contraction and extension. In this mechanism, contractile forces result mostly from motors plucking the filaments transversely rather than buckling them longitudinally. These findings sheds light on recent $\textit{in vitro}$ experiments, and provides a new geometrical understanding of contractility in the myriad of disordered actomyosin systems found $\textit{in vivo}$.
    Physical Review X 07/2014; 4(4). DOI:10.1103/PhysRevX.4.041002 · 9.04 Impact Factor
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    ABSTRACT: Contractile actomyosin bundles are critical for numerous aspects of muscle and nonmuscle cell physiology. Due to the varying composition and structure of actomyosin bundles in vivo, the minimal requirements for their contraction remain unclear. Here, we demonstrate that actin filaments and filaments of smooth muscle myosin motors can self-assemble into bundles with contractile elements that efficiently transmit actomyosin forces to cellular length scales. The contractile and force-generating potential of these minimal actomyosin bundles is sharply sensitive to the myosin density. Above a critical myosin density, these bundles are contractile and generate large tensile forces. Below this threshold, insufficient cross-linking of F-actin by myosin thick filaments prevents efficient force transmission and can result in rapid bundle disintegration. For contractile bundles, the rate of contraction decreases as forces build and stalls under loads of ∼0.5 nN. The dependence of contraction speed and stall force on bundle length is consistent with bundle contraction occurring by several contractile elements connected in series. Thus, contraction in reconstituted actomyosin bundles captures essential biophysical characteristics of myofibrils while lacking numerous molecular constituents and structural signatures of sarcomeres. These results provide insight into nonsarcomeric mechanisms of actomyosin contraction found in smooth muscle and nonmuscle cells.
    Biophysical Journal 06/2011; 100(11):2698-705. DOI:10.1016/j.bpj.2011.04.031 · 3.97 Impact Factor
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