Blue Light Switchable Cell–Cell Interactions Provide Reversible and Spatiotemporal Control Towards Bottom-Up Tissue Engineering.
                            
                                blue
                            
                            
                                CRY2/CIB1
                            
                            
                                
                                    MDA-MB-231
                                
                            
                            
                                Control of cell-cell / cell-material interactions
                            
                                Extracellular optogenetics
                            
                            
                            
                            
                            
                        
                        
                        
                        
                            Abstract:
                            Controlling cell–cell interactions is central for understanding key cellular 
processes and bottom-up tissue assembly from single cells. The challenge is 
to control cell–cell interactions dynamically and reversibly with high spati-
otemporal precision noninvasively and sustainably. In this study, cell–cell 
interactions are controlled with visible light using an optogenetic approach by 
expressing the blue light switchable proteins CRY2 or CIBN on the surfaces of 
cells. CRY2 and CIBN expressing cells form specific heterophilic interactions 
under blue light providing precise control in space and time. Further, these 
interactions are reversible in the dark and can be repeatedly and dynamically 
switched on and off. Unlike previous approaches, these genetically encoded 
proteins allow for long-term expression of the interaction domains and 
respond to nontoxic low intensity blue light. In addition, these interactions 
are suitable to assemble cells into 3D multicellular architectures. Overall, this 
approach captures the dynamic and reversible nature of cell–cell interactions 
and controls them noninvasively and sustainably both in space and time. This 
provides a new way of studying cell–cell interactions and assembling cellular 
building blocks into tissues with unmatched flexibility.