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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.
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.
The extracellular matrix (ECM) controls keratinocyte proliferation, migration, and differentiation through β‐integrin signaling. Wound‐healing research requires expanding cells in vitro while maintaining replicative capacity; however, early terminal differentiation under traditional culture conditions limits expansion. Here, a design of experiments approach identifies poly(ethylene glycol)‐based hydrogel formulations with mechanical properties (elastic modulus, E = 20.9 ± 0.56 kPa) and bioactive peptide sequences that mimic the epidermal ECM. These hydrogels enable systematic investigation of the influence of cell‐binding domains from fibronectin (RGDS), laminin (YIGSR), and collagen IV (HepIII) on keratinocyte stemness and β1 integrin expression. Quantification of 14‐day keratin protein expression shows four hydrogels improve stemness compared to standard techniques. Three hydrogels increase β1 integrin expression, demonstrating a positive linear relationship between stemness and β1 integrin expression. Multifactorial statistical analysis predicts an optimal peptide combination ([RGDS] = 0.67 mm, [YIGSR] = 0.13 mm, and [HepIII] = 0.02 mm) for maintaining stemness in vitro. Best‐performing hydrogels exhibit no decrease in Ki‐67‐positive cells compared to standards (15% decrease, day 7 to 14; p < 0.05, Tukey Test). These data demonstrate that precisely designed hydrogel biomaterials direct integrin expression and promote proliferation, improving the regenerative capability of cultured keratinocytes for basic science and translational work.
Invadopodia are involved in cancer invasion by generating mechanical forces and secreting proteolytic enzymes. It is hypothesized that physical forces applied to integrin, especially α 5 β 1 integrin, are strongly associated with the generation of invadopodial forces and protrusive activity of invadopodia; however, their mechanical relationship remains elusive. Here, a new deoxyribonucleic acid-based force probe is developed for mapping α 5 β 1 integrin tension with single-molecule precision. Using this probe, the formation and maturation of invadopodia depending on integrin type and tension are investigated. In addition, the spatio-temporal analysis of the integrin tension map is performed to measure changes in integrin tension and invadopodial force in each stage of invadopodia development. Consequently, it is found that α 5 β 1 integrin tension above 40 pN is critical not only for adhesion but also for the maturation of invadopodia, eventually leading to the generation of a strong invadopodial force greater than 100 pN through α 5 β 1 integrinligand complexes with actomyosin contractility. This biophysical mechanism underlying the invadopodia formation and mechanical activation may provide new insights into cancer invasion and metastasis.
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