Forms, forces, and stem cell fate

Abstract

Cells change their shape and mechanics dramatically during development and tissue healing in response to morphogens, cell-cell contact, adhesion to extracellular matrix, and more. Several regulatory links have been described between cell shape, cytoskeletal tension, matrix adhesiveness and stiffness, and recent studies have begun to uncover how these mechanotransduction pathways can impact transcriptional signaling and cell fate decision. The integrated mechanisms linking cell forces, form and fate are likely critical for driving normal morphogenesis, tissue development, and healing. Dysregulation of these mechanisms may also tip the scale from normal to diseased states. Here, we highlight mechanisms that alter cell shape and mechanics, and the pathways affected by these changes.

Figure 1. Cell shape dynamics as a regulator of cell fate

Regulation of cell shape is a complex and dynamic process. Classically, in vitro cell shape was thought to be the output of variables such as adhesive ligands or more recently substrate stiffness, while the field of clinical pathology uses cell shape as a histological marker of normal versus diseased cells. During development, morphogenic cues, alignment and tension drive cell shape changes to create new tissues and organs. Using engineering approaches, such as limiting adhesion or altering stiffness, we can modulate cell shape to alter the cell’s mechanics (arrows A or C) for example via Rho mediated tension or actin reorganization, which in turn can regulate transcriptional activity to drive cell fate (D). Alternatively, changes to cell’s environment during disease or healing changes cell shape (C), possibly exacerbating initial pathology (C - E). It is also possible to imagine that transcriptional changes alter the cell’s mechanics (D - F - C), stiffening the local environment, leading to cell shape changes.