title: Molecular mechanochemistry: low force switch slows enzymatic cleavage of human type I collagen monomer.
abstract: In vertebrate animals, fibrillar collagen accumulates, organizes, and persists in structures which resist mechanical force. This antidissipative behavior is possibly due to a mechanochemical force-switch which converts collagen from enzyme-susceptible to enzyme-resistant. Degradation experiments on native tissue and reconstituted fibrils suggest that collagen/enzyme kinetics favor the retention of loaded collagen. We used a massively parallel, single molecule, mechanochemical reaction assay to demonstrate that the effect is derivative of molecular mechanics. Tensile loads higher than 3 pN dramatically reduced (10×) the enzymatic degradation rate of recombinant human type I collagen monomers by Clostridium histolyticum compared to unloaded controls. Because bacterial collagenase accesses collagen at multiple sites and is an aggressive cleaver of the collagen triple helical domain, the results suggest that collagen molecular architecture is generally more stable when mechanically strained in tension. Thus the tensile mechanical state of collagen monomers is likely to be correlated to their longevity in tissues. Further, strain-actuated molecular stability of collagen may constitute the fundamental basis of a smart structural mechanism which enhances the ability of animals to place, retain, and load-optimize material in the path of mechanical forces.
authors.affiliation: Department of Mechanical and Industrial Engineering, Northeastern University, 360 Huntington Avenue, Boston, Massuachusetts 02115, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Camp
authors.forename: Melody
authors.initials: M
authors.lastname: Liles
authors.forename: John
authors.initials: J
authors.lastname: Beale
authors.forename: Nima
authors.initials: N
authors.lastname: Saeidi
authors.forename: Brendan P
authors.initials: BP
authors.lastname: Flynn
authors.forename: Elias
authors.initials: E
authors.lastname: Moore
authors.forename: Shashi K
authors.initials: SK
authors.lastname: Murthy
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Ruberti
mesh_terms: D024042:Collagen Type I / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics
chemical_list: D024042:Collagen Type I