title: Mechanical strain stabilizes reconstituted collagen fibrils against enzymatic degradation by mammalian collagenase matrix metalloproteinase 8 (MMP-8).
abstract: BACKGROUND
  Collagen, a triple-helical, self-organizing protein, is the predominant structural protein in mammals. It is found in bone, ligament, tendon, cartilage, intervertebral disc, skin, blood vessel, and cornea. We have recently postulated that fibrillar collagens (and their complementary enzymes) comprise the basis of a smart structural system which appears to support the retention of molecules in fibrils which are under tensile mechanical strain. The theory suggests that the mechanisms which drive the preferential accumulation of collagen in loaded tissue operate at the molecular level and are not solely cell-driven. The concept reduces control of matrix morphology to an interaction between molecules and the most relevant, physical, and persistent signal: mechanical strain.
  
  
  RESULTS
  The investigation was carried out in an environmentally-controlled microbioreactor in which reconstituted type I collagen micronetworks were gently strained between micropipettes. The strained micronetworks were exposed to active matrix metalloproteinase 8 (MMP-8) and relative degradation rates for loaded and unloaded fibrils were tracked simultaneously using label-free differential interference contrast (DIC) imaging. It was found that applied tensile mechanical strain significantly increased degradation time of loaded fibrils compared to unloaded, paired controls. In many cases, strained fibrils were detectable long after unstrained fibrils were degraded.
  
  
  CONCLUSIONS
  In this investigation we demonstrate for the first time that applied mechanical strain preferentially preserves collagen fibrils in the presence of a physiologically-important mammalian enzyme: MMP-8. These results have the potential to contribute to our understanding of many collagen matrix phenomena including development, adaptation, remodeling and disease. Additionally, tissue engineering could benefit from the ability to sculpt desired structures from physiologically compatible and mutable collagen.
authors.affiliation: Mechanical and Industrial Engineering, Northeastern University, Boston, Massachusetts, United States of America.
authors.forename: Brendan P
authors.initials: BP
authors.lastname: Flynn
authors.forename: Amit P
authors.initials: AP
authors.lastname: Bhole
authors.forename: Nima
authors.initials: N
authors.lastname: Saeidi
authors.forename: Melody
authors.initials: M
authors.lastname: Liles
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dimarzio
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Ruberti
mesh_terms: D000818:Animals; D002417:Cattle; D003094:Collagen / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism*; D057054:Molecular Imaging; D055550:Protein Stability; D013314:Stress, Mechanical; D013379:Substrate Specificity
chemical_list: D003094:Collagen; D020784:Matrix Metalloproteinase 8
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