title: Dynamic force sensing of filamin revealed in single-molecule experiments.
abstract: Mechanical forces are important signals for cell response and development, but detailed molecular mechanisms of force sensing are largely unexplored. The cytoskeletal protein filamin is a key connecting element between the cytoskeleton and transmembrane complexes such as integrins or the von Willebrand receptor glycoprotein Ib. Here, we show using single-molecule mechanical measurements that the recently reported Ig domain pair 20-21 of human filamin A acts as an autoinhibited force-activatable mechanosensor. We developed a mechanical single-molecule competition assay that allows online observation of binding events of target peptides in solution to the strained domain pair. We find that filamin force sensing is a highly dynamic process occurring in rapid equilibrium that increases the affinity to the target peptides by up to a factor of 17 between 2 and 5 pN. The equilibrium mechanism we find here can offer a general scheme for cellular force sensing.
authors.affiliation: Physik Department E22,  Technische Universität München, 85748 Garching,  Germany.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Rognoni
authors.forename: Johannes
authors.initials: J
authors.lastname: Stigler
authors.forename: Benjamin
authors.initials: B
authors.lastname: Pelz
authors.forename: Jari
authors.initials: J
authors.lastname: Ylänne
authors.forename: Matthias
authors.initials: M
authors.lastname: Rief
mesh_terms: D003285:Contractile Proteins / Q000737:chemistry* / Q000378:metabolism; D064448:Filamins; D006801:Humans; D008024:Ligands; D008840:Microfilament Proteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D008024:Ligands; D008840:Microfilament Proteins