Tissue mechanics regulates form, function, and dysfunction

Abstract

Morphogenesis encompasses the developmental processes that reorganize groups of cells into functional tissues and organs. The spatiotemporal patterning of individual cell behaviors is influenced by how cells perceive and respond to mechanical forces, and determines final tissue architecture. Here, we review recent work examining the physical mechanisms of tissue morphogenesis in vertebrate and invertebrate models, discuss how epithelial cells employ contractility to induce global changes that lead to tissue folding, and describe how tissue form itself regulates cell behavior. We then highlight novel tools to recapitulate these processes in engineered tissues.

Figure 1. Tissue folding arises in response to cellular contractility and physical constraints imposed by the tissue microenvironment

A. Domain branching in the chicken lung is preceded by apical constriction [18]. B. In Drosophila, apoptotic cells pull the leg epithelium in the apicobasal direction to drive folding [24] C. The Drosophila egg chamber elongation is driven by stiffness gradients present in the BM [29]. D. Branching in the chicken lung is initiated by FAK and the extension of branches is accompanied by BM remodeling (Spurlin et al., 2018).

Figure 2. Branching morphogenesis is regulated by mechanical forces imposed by its surrounding microenvironment

A. Airway branching in the mouse lung is accompanied by localized smooth muscle differentiation at bifurcating tips [34] and stratification of the epithelium during domain branching B. The branching rate of the murine airway epithelium can be modulated using a microfluidic transmural pressure device [37]