Quantifying cellular and subcellular stretches in embryonic lung epithelia under peristalsis: where to look for...

Peristalsis begins in the lung as soon as the smooth muscle (SM) forms, and persists until birth. As the prenatal lung is filled with liquid, SM action can, through lumen pressure, deform tissues far from the immediately adjacent tissues. Stretching of embryonic tissues has been shown to have potent morphogenetic effects. We hypothesize that these effects are at work in lung morphogenesis. In order to refine that broad hypothesis in a quantitative framework, we geometrically analyse cell shapes in an epithelial tissue, and individual cell deformations resulting from peristaltic waves that completely occlude the airway. Typical distortions can be very large, with opposite orientations in the stalk and tip regions. Apical distortions are always greater than basal distortions. We give a quantitative estimate of the relationship between length of occluded airway and the resulting tissue stretch in the distal tip. We refine our analysis of cell stresses and strains from peristalsis with a simple mechanical model of deformation of cells within an epithelium, which accounts for basic subcellular geometry and material properties. The model identifies likely stress concentrations near the nucleus and at the apical cell-cell junction. The surprisingly large strains of airway peristalsis may serve to rearrange cells and stimulate other mechanosensitive processes by repeatedly aligning cytoskeletal components and/or breaking and reforming lateral cell-cell adhesions. Stress concentrations between nuclei of adjacent cells may serve as a mechanical control mechanism guiding the alignment of nuclei as an epithelium matures.