Physical stimuli-responsive cell-free protein synthesis

Cell-free protein synthesis has been developed as a critical platform in synthetic biology. Unlike the cell-based synthesis system, cell-free system activates transcriptional and translational mechanisms in vitro, and can control protein synthesis by artificially adding components or chemicals. However, the control method puts forward higher requirements in terms of accurate and non-toxic control, which cannot be achieved by chemical substances. For cell-free system, physical signal is a kind of ideal spatiotemporal control approach to replace chemical substances, realizing high accuracy with little side effect. Here we review the methods of using physical signals to control gene expression in cell-free systems, including studies based on light, temperature, electric field, and magnetic force. The transfer of these switches into cell-free system further expands the flexibility and controllability of the system, thus further expanding the application capability of cell-free systems. Finally, existing problems such as signal source and signal transmission are discussed, and future applications in pharmaceutical production, delivery and industrial production are further looked into.