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.

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Supramolecular interactions between the host cucurbit[8]uril (CB[8]) and amino acids have been widely interrogated, but recognition of specific motifs within a protein domain have never been reported. A phage display approach was herein used to select motifs with the highest binding affinity for the heteroternary complex with methyl viologen and CB[8] (MV⋅CB[8]) within a vast pool of cyclic peptide sequences. From the selected motifs, an epitope consisting of three amino acid was extrapolated and incorporated into a solvent-exposed loop of a protein domain; the protein exhibited micromolar binding affinity for the MV⋅CB[8] complex, matching that of the cyclic peptide. By achieving selective CB[8]-mediated conjugation of a small molecule to a recombinant protein scaffold we pave the way to biomedical applications of this simple ternary system.

Remote‐controlled drug depots represent a highly valuable tool for the timely controlled administration of pharmaceuticals in a patient compliant manner. Here, the first pharmacologically controlled material that allows for the scheduled induction of a medical response in mice is described. To this aim, a novel, humanized biohybrid material that releases its cargo in response to a small‐molecule stimulus licensed for human use is developed. The functionality of the material in mice is demonstrated by the remote‐controlled delivery of a vaccine against the oncogenic human papillomavirus type 16. It is shown that the biohybrid depot‐mediated immunoprotection is equivalent to the classical multi‐injection‐based vaccination. These results indicate that this material can be used as a universal remote‐controlled vehicle for the patient‐compliant delivery of vaccines and pharmaceuticals.

Interactive materials that specifically respond to environmental stimuli hold high promise as energy‐autonomous sensors and actuators in biomedicine, analytics or microsystems engineering. However, the implementation of materials specifically responsive to a given small molecule has so far been hampered by a lack of generically applicable stimulus sensors. In this study, a novel and likely general strategy for the synthesis of biohybrid materials with desired stimulus specificity is established. The strategy is based on allosterically regulated DNA‐binding proteins, a conserved protein family that has evolved in prokaryotes to sense and respond to most diverse molecules in order to enable bacterial survival in a changing environment. The novel hydrogel design concept is demonstrated with the example of single‐chain TetR, a protein that binds the tetO DNA motif and dissociates thereof in the presence of the antibiotic tetracycline. Therefore, linear polyacrylamide is crosslinked via the TetR/tetO interaction to a biohybrid material that can subsequently be dissolved by tetracycline in a dose‐dependent manner. This drug‐induced dissolution is applied for the adjustable release of the cytokine interleukin 4 in a tetracycline‐dependent manner. The design concept developed in this study might serve as a blueprint for the synthesis of biohybrid materials responsive to drugs, metabolites or toxins by replacing TetR/tetO with another protein/DNA pair showing the desired stimulus specificity.