https://www.cell.com/cell/pdf/S0092-8674(13)00573-4.pdf

Forces in Tissue Morphogenesis and Patterning

Cells moving in a tissue undergo a rigidity transition resembling that of active particles jamming at a critical density—but the tissue density stays constant. A new type of rigidity transition implicates the physical properties of the cells.

A density-independent rigidity transition in biological tissues

Epithelia are robust tissues that support the structure of embryos and organs and serve as effective barriers against pathogens. Epithelia also chemically separate different physiological environments. These vital functions require tight association between cells through the assembly of junctions that mechanically stabilize the tissue. Remarkably, epithelia are also dynamic and can display a fluid behavior. Cells continuously die or divide, thereby allowing functional tissue homeostasis. Epithelial cells can change shape or intercalate as tissues deform during morphogenesis. We review the mechanical basis of tissue robustness and fluidity, with an emphasis on the pivotal role of junction dynamics. Tissue fluidity emerges from local active stresses acting at cell interfaces and allows the maintenance of epithelial organization during morphogenesis and tissue renewal.

https://science.sciencemag.org/content/sci/340/6137/1185.full.pdf

Mechanics of epithelial tissue homeostasis and morphogenesis.

Obesity, diabetes, and related manifestations are associated with an enhanced, but poorly understood, risk for mucosal infection and systemic inflammation. Here, we show in mouse models of obesity and diabetes that hyperglycemia drives intestinal barrier permeability, through GLUT2-dependent transcriptional reprogramming of intestinal epithelial cells and alteration of tight and adherence junction integrity. Consequently, hyperglycemia-mediated barrier disruption leads to systemic influx of microbial products and enhanced dissemination of enteric infection. Treatment of hyperglycemia, intestinal epithelial-specific GLUT2 deletion, or inhibition of glucose metabolism restores barrier function and bacterial containment. In humans, systemic influx of intestinal microbiome products correlates with individualized glycemic control, indicated by glycated hemoglobin levels. Together, our results mechanistically link hyperglycemia and intestinal barrier function with systemic infectious and inflammatory consequences of obesity and diabetes.

Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection.

During epithelial morphogenesis, E-cadherin adhesive junctions play an important part in mechanically coupling the contractile cortices of cells together, thereby distributing the stresses that drive cell rearrangements at both local and tissue levels. Here we discuss the concept that cellular contractility and E-cadherin-based adhesion are functionally integrated by biomechanical feedback pathways that operate on molecular, cellular and tissue scales.

Charlène Guillot

Papers

Mechanics of epithelial tissue homeostasis and morphogenesis.

Adhesion Disengagement Uncouples Intrinsic and Extrinsic Forces to Drive Cytokinesis in Epithelial Tissues