Constructing mechanosensitive signalling pathways de novo in synthetic cells

Biological mechanotransduction enables cells to sense and respond to mechanical forces in their local environment through changes in cell structure and gene expression, resulting in downstream changes in cell function. However, the complexity of living systems obfuscates the mechanisms of mechanotransduction, and hence the study of these processes in vitro has been critical in characterising the function of existing mechanosensitive membrane proteins. Synthetic cells are biomolecular compartments that aim to mimic the organisation, functionality and behaviours of biological systems, and represent the next step in the development of in vitro cell models. In recent years, mechanosensitive channels have been incorporated into synthetic cells to create de novo mechanosensitive signalling pathways. Here, I will discuss these developments, from the molecular parts used to construct existing pathways, the functionality of such systems, and potential future directions in engineering synthetic mechanotransduction. The recapitulation of mechanotransduction in synthetic biology will facilitate an improved understanding of biological signalling through the study of molecular interactions across length scales, whilst simultaneously generating new biotechnologies that can be applied as diagnostics, microreactors and therapeutics.