Dynamic force sensing of filamin revealed in single-molecule experiments.
Proc Natl Acad Sci U S A
; 109(48): 19679-84, 2012 Nov 27.
Article
en En
| MEDLINE
| ID: mdl-23150587
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Contráctiles
/
Proteínas de Microfilamentos
Límite:
Humans
Idioma:
En
Año:
2012
Tipo del documento:
Article