Chapter 3.2 - Intracellular Force Measurements in Live Cells With Förster Resonance Energy Transfer–Based Molecular Tension Sensors

Abstract

Mechanical forces dictate various aspects of biological processes from single cells to complex organisms. Understanding the molecular mechanisms of force dynamics requires technologies that can measure these forces in living cells. In the past decade, Förster resonance energy transfer (FRET)-based molecular tension sensors have emerged as an intact, in situ technique for the measurement of mechanical forces in live cells. The new findings enabled by these tension sensors have provided a better understanding of the mechanical architecture and mechanotransduction pathways of the cell and have greatly enriched and reshaped our knowledge of biology and medicine. In this chapter, we first discuss the basics of FRET and the state-of-art measurement methods for FRET imaging in live cells. Moreover, with established experience in live cell tension sensing, we systematically introduce the molecular tension sensors and provide practical guidance on how to design and implement molecular tension sensors for in situ force detection in live cells. Lastly, recent advancements and representative examples in molecule-specific force sensing are reviewed and their potential in mechanotransduction is discussed.