Talin rod domains as mechanochemical switches. (A–C) Each talin rod domain can adopt a number of conformations under different force regimes. (A) Folded bundle at low force. (B) Unfolded string of helices at forces above the mechanical threshold. (C) A fully unfolded polypeptide at high forces. Force-induced domain unfolding leads to a switch in the ligand binding profile of that domain. Complete unfolding at high force will result in a linear polypeptide unable to bind folded-domain ligands or helix-binding ligands. While no ligands for this form have been identified so far, many proteins bind linear peptide motifs.