Dissipation of contractile forces: the missing piece in cell mechanics

Kurzawa, Laëtitia; Vianay, Benoît; Senger, Fabrice; Vignaud, Timothée; Blanchoin, Laurent; Théry, Manuel

doi:10.1091/mbc.e16-09-0672

Cited by 29 publications

(25 citation statements)

References 120 publications

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“…The tension in SFs tends to reflect the mechanics of the environment in which cells are embedded. Cells growing in rigid matrices or within tissues that are being stretched build F-actin networks under increased tension 20,43,44 . Recent work has shown that matrix mechanics controls the nuclear localization of the LIM protein FHL2 45 .…”

Section: Discussionmentioning

confidence: 99%

Evolutionarily diverse LIM domain-containing proteins bind stressed actin filaments through a conserved mechanism

Winkelman

Anderson

Suarez

et al. 2020

Preprint

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The actin cytoskeleton assembles into diverse load-bearing networks including stress fibers, muscle sarcomeres, and the cytokinetic ring to both generate and sense mechanical forces. The LIM (Lin11, Isl-1 & Mec-3) domain family is functionally diverse, but most members can associate with the actin cytoskeleton with apparent force-sensitivity. Zyxin rapidly localizes via its LIM domains to failing stress fibers in cells, known as strain sites, to initiate stress fiber repair and maintain mechanical homeostasis. The mechanism by which these LIM domains associate with stress fiber strain sites is not known. Additionally, it is unknown how widespread strain sensing is within the LIM protein family. We observe that many, but not all, LIM domains from functionally diverse proteins localize to spontaneous or induced stress fiber strain sites in mammalian cells. Additionally, the LIM domain region from the fission yeast protein paxillin like 1 (Pxl1) also localizes to stress fiber strain sites in mammalian cells, suggesting that the strain sensing mechanism is ancient and highly conserved. Sequence analysis and mutagenesis of the LIM domain region of zyxin indicate a requirement of tandem LIM domains, which contribute additively, for sensing stress fiber strain sites. In vitro, purified LIM domains from mammalian zyxin and fission yeast Pxl1 bind to mechanically stressed F-actin networks but do not associate with relaxed actin filaments. We propose that tandem LIM domains recognize an F-actin conformation that is rare in the relaxed state but is enriched in the presence of mechanical stress. Cells are subject to a wide range of omnipresent mechanical stimuli, which play essential physiological roles. Epithelial tissue stretch modulates cell proliferation 1,2 , blood pressure regulates the contractility of endothelial cells within blood vessels 3,4 , and muscle contraction shapes connective tissue remodeling 5 . Such mechanotransduction pathways allow for the integration of mechanical cues with the biochemical and genetic circuitry of the cell. While much progress has been made to elucidate the importance of mechanical stimuli in cell physiology, the underlying force-sensing mechanisms and organizational logic of many mechanotransduction pathways are unknown.To respond to mechanical cues and dynamically modulate cell mechanics, the actin cytoskeleton exploits force-sensitive biochemistry to construct actin filament (F-actin)-based network assemblies. Focal adhesions, the adhesive organelles between cells and their external matrix, can change in composition and size under varied mechanical load 6 . At the molecular scale, these focal adhesion changes arise primarily from force-dependent modulation of constituent proteins 6-8 . The force-dependent association of the focal adhesion proteins, vinculin and talin, to actin filaments is sensitive to filament polarity 9,10 , providing a mechanism to guide local cytoskeletal architecture under load. Protrusive forces at the leading edge of migrating cells are generated by actin po...

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Section: Discussionmentioning

confidence: 99%

Evolutionarily diverse LIM domain-containing proteins bind stressed actin filaments through a conserved mechanism

Winkelman

Anderson

Suarez

et al. 2020

Preprint

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“…where G * represents actin with no bound nucleotide. Following [39], this reaction is approximated as a one-step irreversible reaction with ATP and ADP included explicitly, Equation 33. We can write the rate k nex of this approximate reaction as:…”

Section: • Nucleotide Exchangementioning

confidence: 99%

Quantifying dissipation in actomyosin networks

2019

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Quantifying entropy production in various active matter phases will open new avenues for probing self-organization principles in these far-from-equilibrium systems. It has been hypothesized that the dissipation of free energy by active matter systems may be optimized, leading to system trajectories with histories of large dissipation and an accompanying emergence of ordered dynamical states. This interesting idea has not been widely tested. In particular, it is not clear whether emergent states of actomyosin networks, which represent a salient example of biological active matter, self-organize following the principle of dissipation optimization. In order to start addressing this question using detailed computational modelling, we rely on the MEDYAN simulation platform, which allows simulating active matter networks from fundamental molecular principles. We have extended the capabilities of MEDYAN to allow quantification of the rates of dissipation resulting from chemical reactions and relaxation of mechanical stresses during simulation trajectories. This is done by computing precise changes in Gibbs free energy accompanying chemical reactions using a novel formula and through detailed calculations of instantaneous values of the system’s mechanical energy. We validate our approach with a mean-field model that estimates the rates of dissipation from filament treadmilling. Applying this methodology to the self-organization of small disordered actomyosin networks, we find that compact and highly cross-linked networks tend to allow more efficient transduction of chemical free energy into mechanical energy. In these simple systems, we observe that spontaneous network reorganizations tend to result in a decrease in the total dissipation rate to a low steady-state value. Future studies might carefully test whether the dissipation-driven adaptation hypothesis applies in this instance, as well as in more complex cytoskeletal geometries.

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“…To produce effective morphological changes, the magnitude and spatial distribution of contractile forces must be regulated and integrated over distances that are much longer than individual filaments (Agarwal and Zaidel-Bar, 2019;Murrell et al, 2015). However, the mechanism regulating the production and transmission of local forces throughout the cell is still poorly understood (Burridge and Guilluy, 2016;Kurzawa et al, 2017;Livne and Geiger, 2016). The progress in understanding this integration process has notably been limited by the technical challenges to manipulate the network locally while simultaneously measuring the impact on force production at the level of the entire cell.…”

Section: Introductionmentioning

confidence: 99%

Stress fibers are embedded in a contractile cortical network

Vignaud

Copos

Leterrier

et al. 2020

Preprint

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Contractile actomyosin networks generate intracellular forces essential for the regulation of cell shape, migration, and cell-fate decisions, ultimately leading to the remodeling and patterning of tissues. Although actin filaments aligned in bundles represent the main source of traction-force production in adherent cells, there is increasing evidence that these bundles form interconnected and interconvertible structures with the rest of the intracellular actin network. In this study, we explored how these bundles are connected to the surrounding cortical network and the mechanical impact of these interconnected structures on the production and distribution of traction forces on the extracellular matrix and throughout the cell. By using a combination of hydrogel micropatterning, traction-force microscopy and laser photoablation, we measured the relaxation of the cellular traction field in response to local photoablations at various positions within the cell. Our experimental results and modeling of the mechanical response of the network revealed that bundles were fully embedded along their entire length in a continuous and contractile network of cortical filaments. Moreover, the propagation of the contraction of these bundles throughout the entire cell was dependent on this embedding. In addition, these bundles appeared to originate from the alignment and coalescence of thin and unattached cortical actin filaments from the surrounding mesh.

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Dissipation of contractile forces: the missing piece in cell mechanics

Cited by 29 publications

References 120 publications

Evolutionarily diverse LIM domain-containing proteins bind stressed actin filaments through a conserved mechanism

Evolutionarily diverse LIM domain-containing proteins bind stressed actin filaments through a conserved mechanism

Quantifying dissipation in actomyosin networks

Stress fibers are embedded in a contractile cortical network

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