Cooperation of dual modes of cell motility promotes epithelial stress relaxation to accelerate wound healing

Staddon, Michael F.; Bi, Dapeng; Tabatabai, A. Pasha; Ajeti, Visar; Murrell, Michael P.; Banerjee, Shiladitya

doi:10.1371/journal.pcbi.1006502

Cited by 63 publications

(60 citation statements)

References 62 publications

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“…When τ T 1 is small, the cell motion is nearly ballis- tic at short times and diffusive at long times ( ∆r(t) 2 ∝ t) as expected in a typical viscoelastic fluid. This situation corresponds to nearly instantaneous T1 events typically considered previously [29,34,35,38]. Here the F s (q,t) decays sharply with a single timescale of relaxation indicating the tissue fluidizes quickly due to motility ( Fig.…”

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confidence: 71%

Controlled neighbor exchanges drive glassy behavior, intermittency and cell streaming in epithelial tissues

Das

Sastry

2020

Preprint

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Cell neighbor exchanges are integral to tissue rearrangements in biology, including development and repair. Often these processes occur via topological T1 transitions analogous to those observed in foams, grains and colloids. However, in contrast to in non-living materials the T1 transitions in biological tissues are rate-limited and cannot occur instantaneously due to the finite time required to remodel complex structures at cell-cell junctions. Here we study how this rate-limiting process affects the mechanics and collective behavior of cells in a tissue by introducing this important biological constraint in a theoretical vertex-based model as an intrinsic single-cell property. We report in the absence of this time constraint, the tissue undergoes a motility-driven glass transition characterized by a sharp increase in the intermittency of cell-cell rearrangements. Remarkably, this glass transition disappears as T1 transitions are temporally limited. As a unique consequence of limited rearrangements, we also find that the tissue develops spaitally correlated streams of fast and slow cells, in which the fast cells organize into stream-like patterns with leader-follower interactions, and maintain optimally stable cell-cell contacts. The predictions of this work is compared with existing in-vivo experiments in Drosophila pupal development. RESULTSModel -Our appropriately modified "dynamic vertex model" (DVM) [37] retains most of the classic features [39,40]. Cells in a 2D epithelial monolayer are described by irregular polygons, defined using vertices, which constitute the

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confidence: 71%

Controlled neighbor exchanges drive glassy behavior, intermittency and cell streaming in epithelial tissues

Das

Sastry

2020

Preprint

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“…Heterogeneity and cellular invasion -Having established the static mechanical properties, we next focus on the effect of the heterotypic microenvironment on cell migration. We use a dynamic vertex model [58,59] to simulate the motion of a single invading cell in the tissue. The invading cell has a propulsive force v 0 along a polarity vector n, which undergoes random rotational diffusion [45,60] at a slow rate.…”

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Mechanical Heterogeneity in Tissues Promotes Rigidity and Controls Cellular Invasion

Das

2019

Phys. Rev. Lett.

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We study the influence of cell-level mechanical heterogeneity in epithelial tissues using a vertex-based model. Heterogeneity in single cell stiffness is introduced as a quenched random variable in the preferred shape index(p 0 ) for each cell. We uncovered a crossover scaling for the tissue shear modulus, suggesting that tissue collective rigidity is controlled by a single parameter f r , which accounts for the fraction of rigid cells. Interestingly, the rigidity onset occurs at f r = 0.21, far below the contact percolation threshold of rigid cells. Due to the separation of rigidity and contact percolations, heterogeneity can enhance tissue rigidity and gives rise to an intermediate solid state. The influence of heterogeneity on tumor invasion dynamics is also investigated. There is an overall impedance of invasion as the tissue becomes more rigid. Invasion can also occur in the intermediate heterogeneous solid state and is characterized by significant spatial-temporal intermittency.

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“…Extensive analyses have reported the key mechanical factors affecting wound closure. 10 The effects of myosin heterogeneity [5,6], purse-string assembly rate [6], or tissue 11 fluidity [4] have been studied. However, far less is known about the contribution of 12 junctional and cell medial contractility and stiffness during closure, and the energy 13 barrier that they may impose during the intercalation process.…”

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“…The modelling of wound healing on substrates using vertex models has been 20 presented for instance in [6,[8][9][10][11], while homogenised continuum models can be found 21 in [12][13][14], which allow the inclusion of myosin and calcium dynamics [13,15]. Due to 22 72 As a result, the whole tissue geometry and connectivity is given by matrices X, T 73 and Y b = {y 1 b , y 2 b , .…”

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Junctional and cytoplasmatic contributions in wound healing

Mosaffa

Tetley

Ferran

et al. 2020

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Wound healing is characterised by the re-epitheliation of a tissue through the activation of contractile forces concentrated mainly at the wound edge. While the formation of an actin purse string has been identified as one of the main mechanisms, far less is known about the effects of the viscoelastic properties of the surrounding cells, and the different contribution of the junctional and cytoplasmic contractilities.In this paper we simulate the wound healing process, resorting to a hybrid vertex model that includes cell boundary and cytoplasmatic contractilities explicitly, together with a differentiated viscoelastic rheology based on an adaptive rest-length. From experimental measurements of the recoil and closure phases of wounds in the Drosophila wing disc epithelium, we fit tissue viscoelastic properties. We then analyse in terms of closure rate and energy requirements the contributions of junctional and cytoplasmatic contractilities.Our results suggest that reduction of junctional stiffness rather than cytoplasmatic stiffness has a more pronounced effect on shortening closure times, and that intercalation rate has a minor effect on the stored energy, but contributes significantly to shortening the healing process, mostly in the later stages. Author summaryWe simulate the wound healing process of epithelia in the absence of substrate. By analysing the recoil process we are able to fit the viscoelastic properties of the monolayer, and study the influence of contractility at junctions and at the interior polymer network. We numerically simulate the whole wound opening and closure process, and inspect which mechanism has a more pronounced effect in terms of energy barrier and wound closure rate. We conclude that while junctional stiffness seems to be more effective than bulk stiffness at speeding up the closure, the increase of intercalation process is the mechanism with the lowest energy cost. February 17, 2020 1/17 1 Wound healing is a fundamental process for maintaining integrity and functionality 2 in epithelia, tissues, and organisms [1]. The most accepted mechanisms for wound 3 closure are Rac-dependent crawling using cell protrusions [2], and the formation of a 4 contractile supra-cellular actomyosin cable at the wound edge (purse-string 5 mechanism) [3]. However, in embryonic and larval tissues, either the elastic substrate is 6not present or no crawling has been observed. In these cases, the first mechanism is 7 absent and closure relies mostly on the actomyosin cable and cell-cell interactions [4], 8 which is the focus of our study in this article. 9Extensive analyses have reported the key mechanical factors affecting wound closure. 10 The effects of myosin heterogeneity [5,6], purse-string assembly rate [6], or tissue 11 fluidity [4] have been studied. However, far less is known about the contribution of 12 junctional and cell medial contractility and stiffness during closure, and the energy 13 barrier that they may impose during the intercalation process. We here simulate 14 wounding of the Drosoph...

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Cooperation of dual modes of cell motility promotes epithelial stress relaxation to accelerate wound healing

Cited by 63 publications

References 62 publications

Controlled neighbor exchanges drive glassy behavior, intermittency and cell streaming in epithelial tissues

Controlled neighbor exchanges drive glassy behavior, intermittency and cell streaming in epithelial tissues

Mechanical Heterogeneity in Tissues Promotes Rigidity and Controls Cellular Invasion

Junctional and cytoplasmatic contributions in wound healing

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