Mechanotransduction: a major regulator of homeostasis and development

A single mutation in a gene dramatically alters the local cell shape and also the global tissue morphology. The organism develops abnormally spherical. In normal development the epithelium appears stretched a long a uniform axis, and the mutation disrupts this process. The mutation results in a decrease in net force within the epithelium. (Adapted with permission from Ref 30. Copyright 2001 Development).

A schematic illustration of some candidates that sense force and propagate the signaling cascade. While this illustration is not an exhaustive list of every candidate known to be sensitive to force, it describes some canonical mechanotransduction pathways, such as through the integrin–cytoskeleton linkage, and through stretch‐sensitive ion channels.

Mechanotransduction can occur in many locations simultaneously within the cell. Forces can be transmitted from the exterior via the extracellular matrix or cell–cell junctions, or directly into structures like the glycocalyx. These transmitted forces can effect membrane fluidity and biochemistry, or propagate further through the cytoskeleton and even deform the nucleus. All of these events may occur in concert and their contribution need not be equivalent or even cooperative.

The varying time and length scales of cellular responses are illustrated in this figure. In general, as time increases so do the macroscopic changes to the organism. The events that characterize short and quick responses, tend to be second messenger cascades or electrochemical. Other changes, such as gene transcription and cell/tissue morphological changes occur on the order of minutes to hours. Finally, if these events continue the final effect is large‐scale changes in tissue organizations and morphological development of the organism. (Adapted with permission from Ref 65. Copyright 2003 BioMed Central).

A generalized epithelial tissue architecture depicting some characteristic epithelial adhesion structures and geometry. The epithelial tissue is polarized with an apical face and a basal face. The apical face functions mainly to import and export. To increase surface area, the membrane is highly folded forming structures called villi and within the villi are even smaller microvilli. At the basal domain is the extracellular matrix that forms the tissue scaffold. Three major cell–cell adhesion structures exist each with different accompanying physiological functions, the tight junctions, adherens junctions, and the septate junctions. All of these junctions also serve as intracellular anchor points for the cytoskeleton, commonly actin, microtubules, and intermediate filaments.