Membrane force reception: mechanosensation in GPCRs and tools to address it

To survive, all organisms must detect and respond to mechanical cues in their environment. Cells are subjected to a plethora of mechanical forces, such as hydrostatic pressure, cell-cell contact, stretch, compression, and shear stress. Mechanosensitive membrane proteins have evolved across all life kingdoms to sense and respond to forces in the membrane. Bacterial mechanosensitive ion channels provide a blueprint for understanding the fundamental mechanisms that underpin cellular responses to mechanical signals. Recently, the identification of eukaryotic force transducers, which includes membrane proteins other than channels, has led to the recognition of common structural hallmarks and unified biophysical mechanisms that could potentially link these diverse proteins. Accumulating evidence suggests G protein-coupled receptors (GPCRs) are candidates for pressure sensing in mammals. This review summarises the current knowledge on mechanosensitive GPCRs, describes the tools used to assess their mechanosensitivity, and aims to highlight the key characteristics that link these receptors to established mechanosensors.