Staff member

Cells sense mechanical forces and convert them into biochemical signals - a phenomenon called mechanotransduction, which regulates fundamental processes in health and disease. Cells can also be engineered to have exogenous, artificial mechanotransduction mechanisms; such systems implement a synthetic form of mechanotransduction, which could be applied to revert malignant phenotypes, modulate immunotherapies or to develop diagnostic tools. Here we review the status of the nascent field of synthetic mechanotransduction. First, we summarize the types of molecular mechanism known to be involved in endogenous mechanotransduction. Then, we explain how, by taking inspiration from endogenous systems, synthetic mechanotransduction systems have been developed. In its simpler form, these systems involve the expression of synthetic genes responding to natural force-sensing (mechanosensitive) proteins. In a more advanced form, they also include synthetic mechanosensitive proteins. Additionally, other systems have been developed to control force generation itself, resulting in control of tissue shape and function. Finally, we review general considerations for the design of synthetic mechanotransduction systems, and future challenges and opportunities.

JTD Keywords: Activation, Cell-adhesion, Fluid shear-stress, Force transmission, Integrin, Mechanical-stress, Membrane tension, Notch, Nuclear-envelope, Optogenetic control

The emerging field of synthetic developmental biology proposes bottom-up approaches to examine the contribution of each cellular process to complex morphogenesis. However, the shortage of tools to manipulate three-dimensional (3D) shapes of mammalian tissues hinders the progress of the field. Here we report the development of OptoShroom3, an optogenetic tool that achieves fast spatiotemporal control of apical constriction in mammalian epithelia. Activation of OptoShroom3 through illumination in an epithelial Madin-Darby Canine Kidney (MDCK) cell sheet reduces the apical surface of the stimulated cells and causes displacements in the adjacent regions. Light-induced apical constriction provokes the folding of epithelial cell colonies on soft gels. Its application to murine and human neural organoids leads to thickening of neuroepithelia, apical lumen reduction in optic vesicles, and flattening in neuroectodermal tissues. These results show that spatiotemporal control of apical constriction can trigger several types of 3D deformation depending on the initial tissue context.© 2022. The Author(s).

JTD Keywords: build, developmental biology, disease, light, localization, multicellular structures, organization, plate, shroom, Epithelial-cell shape