Investigating the nature of active forces in tissues reveals how contractile cells can form extensile monolayers

Balasubramaniam, Lakshmi; Doostmohammadi, Amin; Saw, Thuan Beng; Narayana, Gautham Hari Narayana Sankara; Mueller, Romain; Dang, Tien; Thomas, Minnah; Gupta, Shafali; Sonam, Surabhi; Yap, Alpha; Toyama, Yusuke; Mège, René-Marc; Yeomans, J. M.; Ladoux, Benoît

doi:10.1038/s41563-021-00919-2

Cited by 98 publications

(151 citation statements)

References 74 publications

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“…contractile in fibroblasts [11] and extensile in epithelial monolayers [10]. Recently it has even been shown that perturbing the adhesion between cells can result in a switch between extensile and contractile behaviours in epithelial cell layers [21]. While the emergence of extensile or contractile behaviour of topological defects has been widely associated to the activity of these systems, here we show that fluctuations can lead to similar patterns of flows around topological defects and result in both extensile and contractile defect behaviour.…”

supporting

confidence: 49%

Fluctuation-induced dynamics of nematic topological defects

Bonn¹,

Ardaševa²,

Mueller³

et al. 2022

Preprint

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supporting

confidence: 49%

Fluctuation-induced dynamics of nematic topological defects

Bonn¹,

Ardaševa²,

Mueller³

et al. 2022

Preprint

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“…Detecting orientational order in epithelia [1,2] has been the focus of several recent studies [3][4][5][6]. The task is commonly approached by tracking the longitudinal direction of individual cells by diagonalizing a rank−2 tensor − i.e.…”

mentioning

confidence: 99%

Epithelia are multiscale active liquid crystals

Armengol-Collado

Carenza

Eckert

et al. 2022

Preprint

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Biological processes such as embryogenesis, wound healing and cancer progression, crucially rely on the ability of epithelial cells to coordinate their mechanical activity over length scales order of magnitudes larger than the typical cellular size. While regulated by signalling pathways, such as YAP (yes-associated protein), MAPK (mitogen-activated protein kinase) and Wnt, this behavior is believed to additionally hinge on a minimal toolkit of physical mechanisms, of which liquid crystal order is the most promising candidat. Yet, experimental and theoretical studies have given so far inconsistent results in this respect: whereas nematic order is often invoked in the interpretation of experimental data, computational models have instead suggested that hexatic order could in fact emerge in the biologically relevant region of parameter space. In this article we resolve this dilemma. Using a combination of in vitro experiments on Madin-Darby canine kidney cells (MDCK), numerical simulations and analytical work, we demonstrate that both nematic and hexatic order is in fact present in epithelial layers, with the former being dominant at large length scales and the latter at small length scales. In MDCK GII cells on uncoated glass, these different types of liquid crystal order crossover at 34 μm, corresponding approximatively to clusters of 21 cells. Our work sheds light on the emergent organization of living matter, provides a new set of tools for analyzing the structure of epithelia and paves the way toward a comprehensive and predictive mesoscopic theory of tissues.

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“…An intriguing possibility how JAM-A-generated signaling events influences cell–matrix adhesions and traction force generation during collective cell migration is that JAM-A acts as a sensor of mechanical forces during collective cell migration. Studies with collectives of migrating cells both in vitro and in vivo indicate that collective cell migration requires mechanical coordination between neighboring cells, and that mechanical forces are transmitted through cell–cell contacts from leader cells at the edges of migrating colonies to the follower cells in their center over a long range [ 11 – 13 , 15 , 67 ], reviewed in [ 68 , 69 ]. Tension on JAM-A applied through trans-homophilic JAM-A interaction activates RhoA in a Ser285 phosphorylation-dependent manner in CHO cells [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

JAM-A interacts with α3β1 integrin and tetraspanins CD151 and CD9 to regulate collective cell migration of polarized epithelial cells

Thölmann

Seebach

Otani

et al. 2022

Cell. Mol. Life Sci.

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Junctional adhesion molecule (JAM)-A is a cell adhesion receptor localized at epithelial cell–cell contacts with enrichment at the tight junctions. Its role during cell–cell contact formation and epithelial barrier formation has intensively been studied. In contrast, its role during collective cell migration is largely unexplored. Here, we show that JAM-A regulates collective cell migration of polarized epithelial cells. Depletion of JAM-A in MDCK cells enhances the motility of singly migrating cells but reduces cell motility of cells embedded in a collective by impairing the dynamics of cryptic lamellipodia formation. This activity of JAM-A is observed in cells grown on laminin and collagen-I but not on fibronectin or vitronectin. Accordingly, we find that JAM-A exists in a complex with the laminin- and collagen-I-binding α3β1 integrin. We also find that JAM-A interacts with tetraspanins CD151 and CD9, which both interact with α3β1 integrin and regulate α3β1 integrin activity in different contexts. Mapping experiments indicate that JAM-A associates with α3β1 integrin and tetraspanins CD151 and CD9 through its extracellular domain. Similar to depletion of JAM-A, depletion of either α3β1 integrin or tetraspanins CD151 and CD9 in MDCK cells slows down collective cell migration. Our findings suggest that JAM-A exists with α3β1 integrin and tetraspanins CD151 and CD9 in a functional complex to regulate collective cell migration of polarized epithelial cells.

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Investigating the nature of active forces in tissues reveals how contractile cells can form extensile monolayers

Cited by 98 publications

References 74 publications

Fluctuation-induced dynamics of nematic topological defects

Fluctuation-induced dynamics of nematic topological defects

Epithelia are multiscale active liquid crystals

JAM-A interacts with α3β1 integrin and tetraspanins CD151 and CD9 to regulate collective cell migration of polarized epithelial cells

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