1Faculty of Biology, University of Freiburg, Schänzlestr. 1, 79104 Freiburg, Germany.
2Signalling Research Centers BIOSS and CIBSS, University of Freiburg, Schänzlestr. 18, 79104 Freiburg, Germany.
Commun Biol. 2019 Jan 8;2:15. doi: 10.1038/s42003-018-0264-7. eCollection 2019.
Optogenetic approaches have gathered momentum in precisely modulating and interrogating cellular signalling and gene expression. The use of optogenetics on the outer cell surface to interrogate how cells receive stimuli from their environment, however, has so far not reached its full potential. Here we demonstrate the development of an optogenetically regulated membrane receptor-ligand pair exemplified by the optically responsive interaction of an integrin receptor with the extracellular matrix. The system is based on an integrin engineered with a phytochrome-interacting factor domain (OptoIntegrin) and a red light-switchable phytochrome B-functionalized matrix (OptoMatrix). This optogenetic receptor-ligand pair enables light-inducible and -reversible cell-matrix interaction, as well as the controlled activation of downstream mechanosensory signalling pathways. Pioneering the application of optogenetic switches in the extracellular environment of cells, this OptoMatrix-OptoIntegrin system may serve as a blueprint for rendering matrix-receptor interactions amendable to precise control with light.
光遗传学方法在精确调节和研究细胞信号转导和基因表达方面取得了很大进展。然而，将光遗传学应用于细胞外表面来研究细胞如何从环境中接收刺激，迄今尚未充分发挥其潜力。在这里，我们展示了一种经过光遗传学调控的膜受体-配体对的开发，该系统以整合素受体与细胞外基质之间的光响应相互作用为例。该系统基于一种经过工程改造的具有光物理相互作用因子结构域的整合素（OptoIntegrin）和一种红光可切换的植烷醇 B 功能化基质（OptoMatrix）。这种光遗传学受体-配体对能够实现光诱导和可逆的细胞-基质相互作用，以及对下游机械感觉信号通路的控制激活。作为在细胞外环境中应用光遗传学开关的先驱，该 OptoMatrix-OptoIntegrin 系统可以作为一个蓝图，使基质-受体相互作用能够通过光进行精确控制。
