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Kemal Arda Günay Tova L. Ceccato Jason S. Silver Kendra L. Bannister Olivia J. Bednarski Leslie A. Leinwand Kristi S. Anseth 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(29):10017-10021
There is a growing interest in materials that can dynamically change their properties in the presence of cells to study mechanobiology. Herein, we exploit the 365 nm light mediated [4+4] photodimerization of anthracene groups to develop cytocompatible PEG‐based hydrogels with tailorable initial moduli that can be further stiffened. A hydrogel formulation that can stiffen from 10 to 50 kPa, corresponding to the stiffness of a healthy and fibrotic heart, respectively, was prepared. This system was used to monitor the stiffness‐dependent localization of NFAT, a downstream target of intracellular calcium signaling using a reporter in live cardiac fibroblasts (CFbs). NFAT translocates to the nucleus of CFbs on stiffening hydrogels within 6 h, whereas it remains cytoplasmic when the CFbs are cultured on either 10 or 50 kPa static hydrogels. This finding demonstrates how dynamic changes in the mechanical properties of a material can reveal the kinetics of mechanoresponsive cell signaling pathways that may otherwise be missed in cells cultured on static substrates. 相似文献
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Shan Chen Zhifei Xu Wen Yang Xiahui Lin Jingying Li Juan Li Huanghao Yang 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(50):18354-18358
Programming cells to sense multiple inputs and activate cellular signal transduction cascades is of great interest. Although this goal has been achieved through the engineering of genetic circuits using synthetic biology tools, a nongenetic and generic approach remains highly demanded. Herein, we present an aptamer‐controlled logic receptor assembly for modulating cellular signal transduction. Aptamers were engineered as “robotic arms” to capture target receptors (c‐Met and CD71) and a DNA logic assembly functioned as a computer processor to handle multiple inputs. As a result, the DNA assembly brings c‐Met and CD71 into close proximity, thus interfering with the ligand–receptor interactions of c‐Met and inhibiting its functions. Using this principle, a set of logic gates was created that respond to DNA strands or light irradiation, modulating the c‐Met/HGF signal pathways. This simple modular design provides a robust chemical tool for modulating cellular signal transduction. 相似文献
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