关键词: FRET cell-ECM interaction drug-screening live-cell imaging mechanotransduction

来  源:   DOI:10.3389/fbioe.2020.595497   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
Extensive studies have shown that cells can sense and modulate the biomechanical properties of the ECM within their resident microenvironment. Thus, targeting the mechanotransduction signaling pathways provides a promising way for disease intervention. However, how cells perceive these mechanical cues of the microenvironment and transduce them into biochemical signals remains to be answered. Förster or fluorescence resonance energy transfer (FRET) based biosensors are a powerful tool that can be used in live-cell mechanotransduction imaging and mechanopharmacological drug screening. In this review, we will first introduce FRET principle and FRET biosensors, and then, recent advances on the integration of FRET biosensors and mechanobiology in normal and pathophysiological conditions will be discussed. Furthermore, we will summarize the current applications and limitations of FRET biosensors in high-throughput drug screening and the future improvement of FRET biosensors. In summary, FRET biosensors have provided a powerful tool for mechanobiology studies to advance our understanding of how cells and matrices interact, and the mechanopharmacological screening for disease intervention.
摘要:
广泛的研究表明,细胞可以在其常驻微环境中感知和调节ECM的生物力学特性。因此,靶向机械转导信号通路为疾病干预提供了有希望的途径.然而,细胞如何感知微环境的这些机械线索并将其转化为生化信号仍有待回答。基于Förster或荧光共振能量转移(FRET)的生物传感器是一种强大的工具,可用于活细胞机械转导成像和机械药理学药物筛选。在这次审查中,我们将首先介绍FRET原理和FRET生物传感器,然后,将讨论在正常和病理生理条件下集成FRET生物传感器和机械生物学的最新进展。此外,我们将总结目前FRET生物传感器在高通量药物筛选中的应用和局限性以及FRET生物传感器的未来改进。总之,FRET生物传感器为机械生物学研究提供了强大的工具,以促进我们对细胞和基质相互作用的理解。以及用于疾病干预的机械药理学筛查。
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