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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.

Application of FRET Biosensors in Mechanobiology and Mechanopharmacological Screening