Active fluidization of polymer networks through molecular motors

Humphrey, David; Duggan, C.; Saha, Devashree; Smith, Dennis W.; Käs, Josef A.

doi:10.1038/416413a

Cited by 281 publications

(189 citation statements)

References 19 publications

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“…While tension levels vary between cells and within a single cell 51 , it is expected that, on average, the tension levels are reduced with BB treatment. The active crosslinker myosin II may also directly play a role in regulating the observed mechanics as shown previously in purified networks 52,53 at intermediate and long timescales. The effect of crosslinking dynamics on relaxation is also readily apparent in the differences in loss tangent (Fig.…”

Section: Figure 3 | the Viscoelastic Properties Of The Cytoplasm Showsupporting

confidence: 52%

Dynamic actin crosslinking governs the cytoplasm’s transition to fluid-like behavior

Chaubet

Chaudhary

Heris

et al. 2019

Preprint

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Cells precisely control their mechanical properties to organize and differentiate into tissues. The architecture and connectivity of cytoskeletal filaments changes in response to mechanical and biochemical cues, allowing the cell to rapidly tune its mechanics from highly-crosslinked, elastic networks to weakly-crosslinked viscous networks. While the role of actin crosslinking in controlling actin network mechanics is clear in purified actin networks, its mechanical role in the cytoplasm of living cells remains unknown. Here, we probe the frequencydependent viscoelastic properties of the cytoplasm in living cells using multiharmonic excitation and in situ optical trap calibration. At previously unexplored long timescales, we observe that the cytoskeleton fluidizes. The mechanics are well-captured by a model in which actin filaments are dynamically connected by a single dominant crosslinker. A disease-causing point mutation (K255E) of the actin crosslinker α-actinin 4 (ACTN4) causes its binding kinetics to be insensitive to tension. Under normal conditions, the viscoelastic properties of wild type (WT) and K255E+/-cells are similar. However, when tension is reduced through myosin II inhibition, WT cells relax 3x faster to the fluid-like regime while K255E+/-cells are not affected. These results indicate that dynamic actin crosslinking enables the cytoplasm to flow at long timescales.

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Section: Figure 3 | the Viscoelastic Properties Of The Cytoplasm Showsupporting

confidence: 52%

Dynamic actin crosslinking governs the cytoplasm’s transition to fluid-like behavior

Chaubet

Chaudhary

Heris

et al. 2019

Preprint

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“…Low crosslink densities as used in this study promote micrometer-scale network contraction and transient build-up of stress. In the absence of crosslinks, motor activity has instead been shown to cause network fluidization [63]. In dilute solutions of bundled actin filaments (below 0.3 mg ml −1 actin), motor activity has been shown to cause superdiffusive motion of the bundles [60,61], as opposed to the sub-diffusive dynamics observed in the entangled networks studied here.…”

Section: Discussionmentioning

confidence: 73%

Time-resolved microrheology of actively remodeling actomyosin networks

et al. 2014

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Living cells constitute an extraordinary state of matter since they are inherently out of thermal equilibrium due to internal metabolic processes. Indeed, measurements of particle motion in the cytoplasm of animal cells have revealed clear signatures of nonthermal fluctuations superposed on passive thermal motion. However, it has been difficult to pinpoint the exact molecular origin of this activity. Here, we employ time-resolved microrheology based on particle tracking to measure nonequilibrium fluctuations produced by myosin motor proteins in a minimal model system composed of purified actin filaments and myosin motors. We show that the motors generate spatially heterogeneous contractile fluctuations, which become less frequent with time as a consequence of motor-driven network remodeling. We analyze the particle tracking data on different length scales, combining particle image velocimetry, an ensemble analysis of the particle trajectories, and finally a kymograph analysis of individual particle trajectories to quantify the length and time scales associated with active particle displacements. All analyses show clear signatures of nonequilibrium activity: the particles exhibit random motion with an enhanced amplitude compared to passive samples, and they exhibit sporadic contractile fluctuations with ballistic motion over large (up to 30 μm) distances. This nonequilibrium activity diminishes with sample age, 3 Equal contribution. New J. Phys. 16 (2014) 075010 M Soares e Silva et al dynamics in minimal cytoskeletal model systems. Active (nonthermal) fluctuations have been observed both for actin networks activated by skeletal muscle myosin II motors [32-36] and in one recent study for nematic microtubule solutions activated by kinesins [37]. Myosin II is a motor protein with two heads that bind to actin filaments and uses chemical energy derived from hydrolysis of adenosine triphosphate (ATP) to generate pN-forces [38]. Individual myosin motors are non-processive, with a duty ratio of only a few per cent at saturating ATP levels. Nevertheless, single-headed myosin II subfragments have been shown to increase the effective temperature of actin networks [39]. Bipolar myosin II filaments, which resemble myosin minifilaments in cells, are more processive and can cause actin network contraction [40][41][42][43]. A combined active and passive microrheology study revealed clear violations of the FDT at low frequencies for active actin-myosin networks [33,34]. Passive microrheology of these networks using video particle tracking revealed clear signatures of nonequilibrium activity in the particle fluctuations. Specifically, the distribution of displacements (or Van Hove correlations) showed a markedly non-Gaussian shape for spherical as well as rod-shaped probe particles [35,36]. In spatially homogeneous networks, non-Gaussianity is indeed a signature of nonthermal activity [44,45]. In crosslinked networks, myosin contractility can generate substantial contractile tension, which can stiffen actin networks by up to 100-fo...

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“…The polymerization of actin filaments with their plus ends oriented towards the plasma membrane is balanced by a myosin-powered, rearward movement of the lamellum actin meshwork known as retrograde flow. The lamellum is less dynamic than the lamellipodium and is characterized by linear actin bundles and mature adhesion sites [116, 117]. In general, NM-2 promotes F-actin anterograde flow in the cell body and retrograde flow in the lamellum [118, 119].…”

Section: Cell Migrationmentioning

confidence: 99%

Nonmuscle myosin-2: mix and match

Heissler

Manstein

2012

Cell. Mol. Life Sci.

198

239

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Members of the nonmuscle myosin-2 (NM-2) family of actin-based molecular motors catalyze the conversion of chemical energy into directed movement and force thereby acting as central regulatory components of the eukaryotic cytoskeleton. By cyclically interacting with adenosine triphosphate and F-actin, NM-2 isoforms promote cytoskeletal force generation in established cellular processes like cell migration, shape changes, adhesion dynamics, endo- and exo-cytosis, and cytokinesis. Novel functions of the NM-2 family members in autophagy and viral infection are emerging, making NM-2 isoforms regulators of nearly all cellular processes that require the spatiotemporal organization of cytoskeletal scaffolding. Here, we assess current views about the role of NM-2 isoforms in these activities including the tight regulation of NM-2 assembly and activation through phosphorylation and how NM-2-mediated changes in cytoskeletal dynamics and mechanics affect cell physiological functions in health and disease.

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Active fluidization of polymer networks through molecular motors

Cited by 281 publications

References 19 publications

Dynamic actin crosslinking governs the cytoplasm’s transition to fluid-like behavior

Dynamic actin crosslinking governs the cytoplasm’s transition to fluid-like behavior

Time-resolved microrheology of actively remodeling actomyosin networks

Nonmuscle myosin-2: mix and match

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