Phytochrome‐Based Extracellular Matrix with Reversibly Tunable Mechanical Properties

Abstract

The mechanical properties of the extracellular environment govern key cellular decision-making processes such as proliferation, differentiation, or migration. [1] Thus, analyzing how cells gauge and interact with their mechanical environment is critical not only for understanding physiological and pathological processes but also for engineering cell and tissue growth and differentiation in regenerative medicine. [2] Although studies using passive elastic or viscoelastic materials have revealed valuable information about cell-matrix interactions, matrices with adjustable mechanical properties more closely reflect the dynamic environments many cells are exposed to in a living organism. [3] In order to recapitulate these dynamic environments, several materials have been developed, which enable the 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, wavelengthspecific, and dose-and space-controlled manner. By integrating engineered cyanobacterial phytochrome 1 into a poly(ethylene 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 mechanosignaling pathways respond to changing mechanical environments and to control the migration of primary immune cells in 3D. This optogenetics-inspired matrix allows fundamental questions of how cells react to dynamic mechanical environments to be addressed. Further, remote control of such matrices can create new opportunities for tissue engineering or provide a basis for optically stimulated drug depots. BiomaterialsThe ORCID identification number(s) for the author(s) of this article can be found under https://doi.

Wavelength‐Dependent Stiffening of Hydrogel Matrices via Redshifted [2+2] Photocycloadditions

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The Role of Photochemical Reactions in the Development of Advanced Soft Materials for Biomedical Applications

“…Due to its ability to form tetramers under cyan light (500 nm) and revert to monomers upon irradiation with violet light (400 nm), this versatile protein can even allow the formation of patterns on hydrogels via stereolithographic techniques . Similar approaches in the reversible formation of hydrogels were reported using the mutant protein Cph1 Y263F, and the pair PhyB FR /PIF . These proteins are able to dimerize under red light (660 nm) and revert back to the monomeric form under NIR light (740 nm).…”

Hydrogels: soft matters in photomedicine

“…An interesting example is the report by Weber and coworkers from earlier this year describing the application of optogenetic with cyanobacterial phytochrome as photoreceptor for tuning the mechanical properties of hydrogels. 507 While applied to investigating mechanosignaling pathways in human mesenchymal stem cells, it also shines a light on possibilities for optically controlled drug depots.…”