OptoProfilin: A Single Component Biosensor of Applied Cellular Stress.
                            
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                                CRY2/CRY2
                            
                            
                                
                                    HEK293T
                                
                            
                                
                                    HeLa
                                
                            
                                
                                    Neuro-2a
                                
                            
                                
                                    NIH/3T3
                                
                            
                            
                                Control of cytoskeleton / cell motility / cell shape
                            
                                Organelle manipulation
                            
                            
                            
                            
                            
                        
                        
                        
                        
                            Abstract:
                            The actin cytoskeleton is a biosensor of cellular stress and a potential prognosticator of human disease. In particular, aberrant cytoskeletal structures such as stress granules formed in response to energetic and oxidative stress are closely linked to ageing, cancer, cardiovascular disease, and viral infection. Whether these cytoskeletal phenomena can be harnessed for the development of biosensors for cytoskeletal dysfunction and, by extension, disease progression, remains an open question. In this work, we describe the design and development of an optogenetic iteration of profilin, an actin monomer binding protein with critical functions in cytoskeletal dynamics. We demonstrate that this optically activated profilin ('OptoProfilin') can act as an optically triggered biosensor of applied cellular stress in select immortalized cell lines. Notably, OptoProfilin is a single component biosensor, likely increasing its utility for experimentalists. While a large body of preexisting work closely links profilin activity with cellular stress and neurodegenerative disease, this, to our knowledge, is the first example of profilin as an optogenetic biosensor of stress-induced changes in the cytoskeleton.