Ricken Julia, Medda Rebecca, Wegner Seraphine V
Max Planck Institute for Polymer Research, Ackermannweg 10, 55128, Mainz, Germany.
Department of Biophysical Chemistry, University of Heidelberg, Im Neuenheimer Feld 253, 69120, Heidelberg, Germany.
Adv Biosyst. 2019 Mar;3(3):e1800302. doi: 10.1002/adbi.201800302. Epub 2019 Jan 29.
The dynamic and spatiotemporal control of integrin-mediated cell adhesion to RGD motifs in its extracellular matrix (ECM) is important for understating cell biology and biomedical applications because cell adhesion fundamentally regulates cellular behavior. Herein, the first photoswitchable synthetic ECM protein, Photo-ECM, based on the blue light switchable protein LOV2 is engineered. The Photo-ECM protein includes a RGD sequence, which is hidden in the folded LOV2 protein structure in the dark and is exposed under blue light so that integrins can bind and cells can adhere. The switchable presentation of the RGD motif allows to reversibly mediate and modulate integrin-based cell adhesions using noninvasive blue light. With this protein cell adhesions in live cells could be reversed and the dynamics at the cellular level is observed. Hence, the Photo-ECM opens a new possibility to investigate the spatiotemporal regulation of cell adhesions in cell biology and is the first step toward a genetically encoded and light-responsive ECM.
整合素介导的细胞与细胞外基质(ECM)中RGD基序的粘附的动态和时空控制对于理解细胞生物学和生物医学应用非常重要,因为细胞粘附从根本上调节细胞行为。在此,基于蓝光可切换蛋白LOV2设计了首个可光开关的合成ECM蛋白,即光控ECM(Photo-ECM)。光控ECM蛋白包含一个RGD序列,该序列在黑暗中隐藏于折叠的LOV2蛋白结构中,在蓝光下暴露,从而使整合素能够结合,细胞能够粘附。RGD基序的可切换呈现使得能够使用无创蓝光可逆地介导和调节基于整合素的细胞粘附。利用这种蛋白,活细胞中的细胞粘附可以被逆转,并观察到细胞水平的动态变化。因此,光控ECM为研究细胞生物学中细胞粘附的时空调节开辟了新的可能性,是迈向基因编码和光响应性ECM的第一步。