Generating artificial organs and tissues from stem cells would revolutionize regenerative medicine and open the door to controllable, biology-based robotics. These systems require a physical understanding of cells, specifically their dynamic and adaptive responses to external forces. This “mechanotransduction” is already known to control important cellular functions, and even stem cell differentiation. With the project proposed here, I plan to bring our quantitative understanding of force-controlled cell functions to a new level by a challenging and novel photomechanical cell stimulation approach. It will combine new materials containing photoswitchable molecules with a complex optical system employing intense laser light pulses. By pulsing the laser, we can apply controllable force stimuli on cells through a conformational change of the photoswitchable molecules. I hypothesize that cell functions, such as adhesion, migration and differentiation, have a huge systematic dependency on frequency, duration, history, and intensity of the force stimuli. Importantly, the method I propose applies forces to cells solely via light and does not require genetic modifications. Using this novel strategy for photomechanical stimulation of cellular proteins, we will be able to collect previously unobtainable physical information within cells on multiple size scales, from the single molecule to tissue level. Using the laser like a pen, we will be able for the first time to write cell functions in 3D, imitating the growth of the cellular scaffolds in living creatures: a completely new means of photomechanically controlling multicellular structures. Ultimately, the tools and materials we study in this interdisciplinary project will allow for the writing of multicellular structures in vitro and in vivo by force-induced mechanotransduction in stem cells. It will lead to a paradigm-shift in many fields, from biophysics to regenerative medicine, synthetic biology and biohybrid robotics.
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