Substrate area confinement is a key determinant of cell velocity in collective migration

Abstract

Collective cell migration is fundamental throughout development, wound healing and in many diseases. Although much effort has focused on cell-cell junctions, a role for physical confinement in collective cell migration remains unclear. Here we used adhesive microstripes of varying widths to mimic the spatial confinement experienced by follower cells within epithelial tissues. Our results reveal that the substrate area confinement is sufficient to modulate the three-dimensional (3D) cellular morphology without the need for intercellular adhesive cues. Our findings show a direct correlation between the migration velocity of confined cells and their cell-substrate adhesive area. Closer examination revealed that adhesive area confinement reduces lamellipodial protrusive forces, decreases the number of focal complexes at the leading edge and prevents the maturation of focal adhesions at the trailing edge, leading together to less effective

Actomyosin contractility scales with myoblast elongation and enhances differentiation through YAP nuclear export

“…PDMS stamps were made hydrophilic under ultraviolet-ozone (UV/O3) expositions for 7 minutes. Then a solution of fibronectin (FN, Millipore Corp.) and poly-l-lysine (PLL, Sigma) was incubated under a sterile hood on the structured side of the stamps for 1 hour 60 . PDMS stamps were gently dried with a nitrogen flow and placed into contact with PDMS coated coverslips or hydroxy-PAAm hydrogels for 30 seconds or 1 hour respectively to obtain adhesive micropatterns of 1600 µm 2 that span a wide range of geometries: circle, square, triangle and rectangle of 1:4 and 1:7 aspect ratios.…”

A free boundary mechanobiological model of epithelial tissues

“…N , to represent the cell boundaries, such that the left boundary of cell i is x i−1 (t) and the right boundary of cell i is x i (t). Epithelial tissues often evolve in confined spaces [39]. Therefore we fix the left tissue boundary at x 0 (t) = 0, while the right tissue boundary is a free boundary, x N (t) = L(t).…”

Innovative Tools for Mechanobiology: Unraveling Outside-In and Inside-Out Mechanotransduction

“…Using μCP, it has been suggested that mechanical interactions between cells and ECM that modulate cytoskeletal tension may therefore play a key role in the control of directional cell motility. In the context of cell migration, μCP was also used to study the influence of the 2D spatial confinement by using adhesive ratchets (Mahmud et al, 2009; Mohammed et al, 2019). Adhesive micropatterns were applied to the study of the influence of the adhesive micro-environment on the actin architecture and contractility (Mandal et al, 2014).…”