Nonautonomous contact guidance signaling during collective cell migration

Abstract

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

Epithelial self-healing is recapitulated by a 3D biomimetic E-cadherin junction

“…3). By contrast, monolayers maintained front-rear polarity and exhibited rapid and directed migration at the inert control MTM, consistent with mechanical "contact guidance"-biased cell migration in response to topographic cues (38,39). Hence, stabilization of hybrid junctions at the Ecad:Fc MTM overrode contact guidance along the MTM and inhibited migration.…”

Collective cell migration: guidance principles and hierarchies

“…Examples of aligned 3D tissue include continuous sheet-like 2D interfaces present between muscle fibers or larger nerves and discontinuous networks formed by ECM fibrils or cell structures, such as neuronal filaments [50,56] (Figure 2C,D and Table 1). As a '2.5D' intermediate, a groove or angled surface (e.g., along the edge of a cell culture dish) provides bilateral guidance whereby apical confinement is lacking [57,58] ( Figure 2E). Thus, in 1D, 2D, and 2.5D haptokinesis adhesion systems guide directionality, whereas 3D guidance additionally follows the path of least resistance defined by multilateral and space-confining extracellular structures [49].…”

Round and round gets you somewhere: collective cell migration and planar polarity in elongating Drosophila egg chambers

“…When migratory mammalian epithelial cells are cultured on micropatterns that contain parallel microgrooves and ridges, their leading edge protrusions preferentially align with the pattern [40]. Likewise, the velocity and coherence of their movement increases [41]. Interaction with a fibrillar ECM also increases the coherence of collectively migrating prechordal plate cells in zebrafish [42].…”