Mechanical Stress as a Regulator of Cytoskeletal Contractility and Nuclear Shape in Embryonic Epithelia

Abstract

The mechano-sensitive responses of the heart and brain were examined in the chick embryo during Hamburger and Hamilton stages 10-12. During these early stages of development, cells in these structures are organized into epithelia. Isolated hearts and brains were compressed by controlled amounts of surface tension (ST) at the surface of the sample, and microindentation was used to measure tissue stiffness following several hours of culture. The response of both organs was qualitatively similar, as they stiffened under reduced loading. With increased loading, however, the brain softened while heart stiffness was similar to controls. In the brain, changes in nuclear shape and morphology correlated with these responses, as nuclei became more elliptical with decreased loading and rounder with increased loading. Exposure to the myosin inhibitor blebbistatin indicated that these changes in stiffness and nuclear shape are likely caused by altered cytoskeletal contraction. Computational modeling suggests that this behavior tends to return peak tissue stress back toward the levels it has in the intact heart and brain. These results suggest that developing cardiac and neural epithelia respond similarly to changes in applied loads by altering contractility in ways that tend to restore the original mechanical stress state. Hence, this study supports the view that stress-based mechanical feedback plays a role in regulating epithelial development.