title: Glycation cross-linking induced mechanical-enzymatic cleavage of microscale tendon fibers.
abstract: Recent molecular modeling data using collagen peptides predicted that mechanical force transmitted through intermolecular cross-links resulted in collagen triple helix unwinding. These simulations further predicted that this unwinding, referred to as triple helical microunfolding, occurred at forces well below canonical collagen damage mechanisms. Based in large part on these data, we hypothesized that mechanical loading of glycation cross-linked tendon microfibers would result in accelerated collagenolytic enzyme damage. This hypothesis is in stark contrast to reports in literature that indicated that individually mechanical loading or cross-linking each retards enzymatic degradation of collagen substrates. Using our Collagen Enzyme Mechano-Kinetic Automated Testing (CEMKAT) System we mechanically loaded collagen-rich tendon microfibers that had been chemically cross-linked with sugar and tested for degrading enzyme susceptibility. Our results indicated that cross-linked fibers were >5 times more resistant to enzymatic degradation while unloaded but became highly susceptible to enzyme cleavage when they were stretched by an applied mechanical deformation.
authors: Laboratory for Soft Tissue Research, Tissue Engineering, Regeneration and Repair Program, Hospital for Special Surgery, 535 East 70th Street, New York, New York 10021, United States; Physiology, Biophysics & Systems Biology Program, Weill Graduate School of Medical Sciences, Cornell University, 1300 York Avenue, New York, New York 10065, United States. Electronic address: BourneJ@HSS.EDU.
authors: Jonathan W
authors: JW
authors: Bourne
authors: Laboratory for Soft Tissue Research, Tissue Engineering, Regeneration and Repair Program, Hospital for Special Surgery, 535 East 70th Street, New York, New York 10021, United States.
authors: Jared M
authors: JM
authors: Lippell
authors: Laboratory for Soft Tissue Research, Tissue Engineering, Regeneration and Repair Program, Hospital for Special Surgery, 535 East 70th Street, New York, New York 10021, United States; Physiology, Biophysics & Systems Biology Program, Weill Graduate School of Medical Sciences, Cornell University, 1300 York Avenue, New York, New York 10065, United States.
authors: Peter A
authors: PA
authors: Torzilli
mesh_terms: D000818:Animals; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism; D006031:Glycosylation; D007700:Kinetics; D055595:Mechanical Phenomena; D020894:Microfibrils / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D051381:Rats; D013314:Stress, Mechanical; D013710:Tendons / Q000737:chemistry / Q000378:metabolism
chemical_list: D003094:Collagen; D017364:Collagenases
keywords: Collagen; Collagenase; Enzyme mechano-kinetic cleavage; Glycation cross-linking; Tendon microfibers