DNA-Based Molecular\nClamp for Probing Protein Interactions and Structure under Force

Cellular mechanotransduction, a process central to cell\nbiology,\nembryogenesis, adult physiology, and multiple diseases, is thought\nto be mediated by force-driven changes in protein conformation that\ncontrol protein function. However, methods to study proteins under\ndefined mechanical loads on a biochemical scale are lacking. We report\nthe development of a DNA-based device in which the transition between\nsingle- and double-stranded DNA applies tension to an attached protein.\nUsing a fragment of the talin rod domain as a test case, negative-stain\nelectron microscopy reveals programmable extension, while pull down\nassays show tension-induced binding to two ligands, ARPC5L and vinculin,\nknown to bind to cryptic sites inside the talin structure. These results\ndemonstrate the utility of the DNA clamp for biochemical studies and\npotential structural analysis.