Double-stranded DNA force sensors to study the molecular level forces required to activate signaling pathways

Abstract

Single-molecule force measurement techniques provide unique opportunities to investigate simple molecular interactions and complicated force-induced cell responses. This has revolutionized our understanding of how mechanical cues influence cell behaviors. Recent advances in DNA technologies have led to the development of tension sensors for high-throughput screening of pN scale forces with single-molecule precision. Thus, the emerging DNA-based mechano-sensors are replacing conventional single-molecule force spectroscopes. This review provides an overview of double-stranded DNA-based mechano-sensors, such as the tension gauge tether (TGT) and its derivatives, and their biophysical applications. First, we review the theoretical background of the force-induced rupture of DNA duplexes and force sensing mechanisms using DNA structures. Next, we survey the use of double-stranded DNA-based force sensors to study the role of mechanical forces, mostly receptor tensions, in signaling pathways.