Phytochrome-based extracellular matrix with reversibly tunable mechanical properties

Interrogation and control of cellular fate and function using optogenetics is providing revolutionary insights into biology. Optogenetic control of cells is achieved by coupling genetically encoded photoreceptors to cellular effectors and enables unprecedented spatiotemporal control of signaling processes. Here, a fast and reversibly switchable photoreceptor is used to tune the mechanical properties of polymer materials in a fully reversible, wavelength-specific, and dose- and space-controlled manner. By integrating engineered cyanobacterial phytochrome 1 into a polyethylene glycol matrix, hydrogel materials responsive to light in the cell-compatible red/far-red spectrum are synthesized. These materials are applied to study in human mesenchymal stem cells how different mechano-signaling pathways respond to changing mechanical environments, and to control the migration of primary immune cells in 3D. This optogenetics-inspired matrix allows addressing fundamental questions of how cells react to dynamic mechanical environments. Further, remote control of such matrices could create new opportunities for tissue engineering or provide a basis for optically stimulated drug depots. Overall design: Analysis of global gene expression changes due to differences in the mechanical properties of the phytochrome-based hydrogels

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Hörner M, Raute K, Hummel B, Madl J, Creusen G, Thomas OS, Christen EH, Hotz N, Gübeli RJ, Engesser R, Rebmann B, Lauer J, Rolauffs B, Timmer J, Schamel WWA, Pruszak J, Römer W, Zurbriggen MD, Friedrich C, Walther A, Minguet S, Sawarkar R, Weber W