Topographical curvature is sufficient to control epithelium elongation

Abstract

How biophysical cues can control tissue morphogenesis is a central question in biology and for the development of efficient tissue engineering strategies. Recent data suggest that specific topographies such as grooves and ridges can trigger anisotropic tissue growth. However, the specific contribution of biologically relevant topographical features such as cell-scale curvature is still unclear. Here we engineer a series of grooves and ridges model topographies exhibiting specific curvature at the ridge/groove junctions and monitored the growth of epithelial colonies on these surfaces. We observe a striking proportionality between the maximum convex curvature of the ridges and the elongation of the epithelium. This is accompanied by the anisotropic distribution of F-actin and nuclei with partial exclusion of both in convex regions as well as the curvature-dependent reorientation of pluricellular protrusions and mitotic spindles. This demonstrates that curvature itself is sufficient to trigger and modulate the oriented growth of epithelia through the formation of convex “topographical barriers” and establishes curvature as a powerful tuning parameter for tissue engineering and biomimetic biomaterial design.

The emergence of spontaneous coordinated epithelial rotation on cylindrical curved surfaces

“…The difference between f -CTs and t -CTs might originate from different cell-substrate interactions due to different curvatures. Previous investigations have demonstrated that cell scale curvature could affect focal adhesion (FA) organization and dynamics ( 43 ), which would profoundly influence pluricellular protrusion orientations ( 44 ) and cell polarity ( 45 ). In our case, it was possible that t -CTs and f -CTs responded to distinct curvatures with different tissue organizations and mechanics.…”

Mechanobiological approaches to synthetic morphogenesis: learning by building

“…They seem to sense curvature through cell thickness, tissue density and nuclear shape and position, and respond by subsequent change in the localization of YAP (lower in high density regions), expression of nuclear lamins and proliferation rate. Cell localization within a migrating epithelial monolayer (leader vs. mid-cluster), as well as the size of the cell cluster [99] and curvature magnitude [100] all affect F-actin and nuclear positioning, excluding both from highly convex regions [100]. Longitudinal groove scaffolds also help orient monolayer growth [100].…”

“…Cell localization within a migrating epithelial monolayer (leader vs. mid-cluster), as well as the size of the cell cluster [99] and curvature magnitude [100] all affect F-actin and nuclear positioning, excluding both from highly convex regions [100]. Longitudinal groove scaffolds also help orient monolayer growth [100]. The intestinal epithelium senses curvature, as well.…”

A Biomimetic High Throughput Model of Cancer Cell Spheroid Dissemination onto Aligned Fibrillar Collagen

“…[7] In this context, the in vivo environment surrounding or associated with the epithelia are edgeless and exhibit fibrillar and curved topographies on the cellular scale. [10] Furthermore, due to the use of synthetic polymer-based materials, these templates exclude ECM remodeling or proteolytic degradation mediated by matrix metalloproteinases to navigate through confined spaces. [11] Therefore, fibrillar and edge-less topographies are needed to investigate cell migration in the context of cell contact-guidance and morphogenesis.…”