Collective cell motion in endothelial monolayers

Szabó, András; Ünnep, Renáta; Méhes, Előd; Twal, Waleed O.; Argraves, W. Scott; Cao, Yuansheng; Czirók, András

doi:10.1088/1478-3975/7/4/046007

Cited by 193 publications

(291 citation statements)

References 49 publications

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“…Many polarity-regulating mechanisms have also been shown to create collective cell migration in simulations. These include extensions of flocking models of birds in which cell polarity (and hence velocity) become aligned with cell neighbor velocities (11,14,18,45), models where polarity becomes aligned with the cell's velocity or displacement (13,15,17,(46)(47)(48), and more directly experimentally inspired mechanisms including contact inhibition of locomotion (10,12). We are interested in studying the role of these polarity-control mechanisms in establishing persistent rotation and cohort migration in these small systems, which may provide a useful testing ground for effects beyond the more universal features of alignment in larger systems.…”

Section: Rotational Motion Is Strongly Regulated By Cell Polarity Mecmentioning

confidence: 99%

Polarity mechanisms such as contact inhibition of locomotion regulate persistent rotational motion of mammalian cells on micropatterns

Camley

Zhang

Zhao

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

146

192

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Pairs of endothelial cells on adhesive micropatterns rotate persistently, but pairs of fibroblasts do not; coherent rotation is present in normal mammary acini and kidney cells but absent in cancerous cells. Why? To answer this question, we develop a computational model of pairs of mammalian cells on adhesive micropatterns using a phase field method and study the conditions under which persistent rotational motion (PRM) emerges. Our model couples the shape of the cell, the cell's internal chemical polarity, and interactions between cells such as volume exclusion and adhesion. We show that PRM can emerge from this minimal model and that the cell-cell interface may be influenced by the nucleus. We study the effect of various cell polarity mechanisms on rotational motion, including contact inhibition of locomotion, neighbor alignment, and velocity alignment, where cells align their polarity to their velocity. These polarity mechanisms strongly regulate PRM: Small differences in polarity mechanisms can create significant differences in collective rotation. We argue that the existence or absence of rotation under confinement may lead to insight into the cell's methods for coordinating collective cell motility. C ollective cell migration is a crucial aspect of wound healing, growth and development of organs and tissues, and cancer invasion (1-3). Cells may move in cohesive groups ranging from small clusters of invading cancerous cells to ducts and branches during morphogenesis to monolayers of epithelial or endothelial cells. Two hallmarks of collective migration are strong cell-cell adhesion and multicellular polarity-an organization of the cellular orientation beyond the single-cell level (1). Cell-cell interactions can lead to collective behavior not evident in any single cell, including chemotaxis in clusters of cells that singly do not chemotax (4). Collective behavior may arise from cell-cell interactions altering the polarity of individual cells (5, 6). Many theories have been proposed for how this multicellular order appears, either in specific biological contexts (7-11) or in simpler, more generic models (12-16). Some authors argue that these dynamics are relatively universal and can be understood with minimal knowledge of the signaling pathways involved (2, 17).Collective rotation is commonly observed in collectively migrating cells, especially in confinement. Persistent rotations have been observed in the slime mold Dictyostelium discoideum (18), canine kidney epithelial cells on adhesive micropatterns (19), and small numbers of endothelial cells on micropatterns (20,21). Transient swirling patterns are also seen in epithelial monolayers (22). Recent work has also observed that the growth of spherical acini of human mammary epithelial cells in 3D matrix involves a coherent rotation persisting from a single cell to several cells; this rotation is not present in randomly motile cancerous cells (23). Similarly, cancerous cells on adhesive micropatterns do not develop coherent rotation (19). In a recent review ...

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Section: Rotational Motion Is Strongly Regulated By Cell Polarity Mecmentioning

confidence: 99%

Polarity mechanisms such as contact inhibition of locomotion regulate persistent rotational motion of mammalian cells on micropatterns

Camley

Zhang

Zhao

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

146

192

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“…The model has similar velocities for cell motion either in isotropic or anisotropic matrices but with an increase in persistence for the latter. It is worth noting that the model proposed in [27] considered only isolated cells interacting with the environment, whereas the model proposed in [30] included a cellular Potts formalism describing collective cell streams in epithelial monolayers [47]. In this case, it was concluded that intercellular adhesion modulated the extent of cell groups undergoing local collective movements in the monolayer.…”

Section: Cell-based Models Describing Experimental Datamentioning

confidence: 99%

Spatio-temporal morphology changes in and quenching effects on the 2D spreading dynamics of cell colonies in both plain and methylcellulose-containing culture media

et al. 2016

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To deal with complex systems, microscopic and global approaches become of particular interest. Our previous results from the dynamics of large cell colonies indicated that their 2D front roughness dynamics is compatible with the standard Kardar-Parisi-Zhang (KPZ) or the quenched KPZ equations either in plain or methylcellulose (MC)-containing gel culture media, respectively. In both cases, the influence of a non-uniform distribution of the colony constituents was significant. These results encouraged us to investigate the overall dynamics of those systems considering the morphology and size, the duplication rate, and the motility of single cells. For this purpose, colonies with different cell populations (N) exhibiting quasi-circular and quasi-linear growth fronts in plain and MC-containing culture media are investigated. For small N, the average radial front velocity and its change with time depend on MC concentration. MC in the medium interferes with cell mitosis, contributes to the local enlargement of cells, and increases the distribution of spatio-temporal cell density heterogeneities. Colony spreading in MC-containing media proceeds under two main quenching effects, I and II; the former mainly depending on the culture medium composition and structure and the latter caused by the distribution of enlarged local cell domains. For large N, colony spreading occurs at constant velocity. The characteristics of cell motility, assessed by measuring their trajectories and the corresponding velocity field, reflect the effect of enlarged, slowmoving cells and the structure of the medium. Local average cell size distribution and individual cell motility data from plain and MC-containing media are qualitatively consistent with the predictions of both the extended cellular Potts models and the observed transition of the front roughness dynamics from a standard KPZ to a quenched KPZ. In this case, quenching J Biol Phys (2016) 42:477-502 DOI 10.1007

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“…To further probe the possibility that the underlying mechanism of signal propagation originates from steric constraints owing to limited free space, we adapted an existing computational model of cell streaming in confluent sheets (8,29,30) to model cell behavior on our hybrid substrates in the parallel case configuration. The main biophysical parameters in the model are (i) membrane energy of cell-cell junctions and any unbound membrane (controlling the cohesion of the cell population) and (ii) the motile force that cells exert on the substrate and persistence of cell polarization.…”

Section: Propagation Of Contact Guidance Signals From a Topographicmentioning

confidence: 99%

Nonautonomous contact guidance signaling during collective cell migration

Londono¹,

Loureiro

Slater

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Directed migration of groups of cells is a critical aspect of tissue morphogenesis that ensures proper tissue organization and, consequently, function. Cells moving in groups, unlike single cells, must coordinate their migratory behavior to maintain tissue integrity. During directed migration, cells are guided by a combination of mechanical and chemical cues presented by neighboring cells and the surrounding extracellular matrix. One important class of signals that guide cell migration includes topographic cues. Although the contact guidance response of individual cells to topographic cues has been extensively characterized, little is known about the response of groups of cells to topographic cues, the impact of such cues on cell-cell coordination within groups, and the transmission of nonautonomous contact guidance information between neighboring cells. Here, we explore these phenomena by quantifying the migratory response of confluent monolayers of epithelial and fibroblast cells to contact guidance cues provided by grooved topography. We show that, in both sparse clusters and confluent sheets, individual cells are contactguided by grooves and show more coordinated behavior on grooved versus flat substrates. Furthermore, we demonstrate both in vitro and in silico that the guidance signal provided by a groove can propagate between neighboring cells in a confluent monolayer, and that the distance over which signal propagation occurs is not significantly influenced by the strength of cell-cell junctions but is an emergent property, similar to cellular streaming, triggered by mechanical exclusion interactions within the collective system. correlation length | emergent behavior | mechanical signal propagation | group coordination

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Collective cell motion in endothelial monolayers

Cited by 193 publications

References 49 publications

Polarity mechanisms such as contact inhibition of locomotion regulate persistent rotational motion of mammalian cells on micropatterns

Polarity mechanisms such as contact inhibition of locomotion regulate persistent rotational motion of mammalian cells on micropatterns

Spatio-temporal morphology changes in and quenching effects on the 2D spreading dynamics of cell colonies in both plain and methylcellulose-containing culture media

Nonautonomous contact guidance signaling during collective cell migration

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