Jeffery W. Ruberti
Shashi K. Murthy, Mark Williams, Constantinos Mavroidis
Date of Award
Doctor of Philosophy
Department or Academic Unit
College of Engineering. Department of Mechanical and Industrial Engineering.
Collagen, Collagenase, Extracellular Matrix, Matrix Metalloproteinase, Mechanochemistry, Single Molecule
Engineering | Mechanical Engineering
In nature it can be observed that collagen, specifically type I collagen, forms structures in vertebrate animals that resist mechanical loading. The method of load-optimization for these collagen structures is currently unknown. We propose that the method of optimization is based on a low force switch that slows the rate of enzymatic degradation of type I collagen. To investigate this phenomenon, we developed a low cost, massively parallel magnetic tweezer setup that allowed us to apply small amounts of force on many single type I collagen monomers simultaneously. The application of a force of at least 3pN, significantly slows the enzymatic cleavage rate of clostridium histolyticum collagenase by an order of magnitude. This is shown at multiple temperatures and at multiple enzyme concentrations above the Micheals-Menten constant. Initial results indicate that a small application of force also slows the enzymatic cleavage rate of matrix metalloproteinase-8. These results disprove the null hypotheses that mechanical force increases enzymatic activity and suggest that the triple helix portion of the type I collagen monomer is more stable while loaded.
Robert James Camp
Camp, Robert James, "Quantifying the mechanosensitivity of the type I collagen monomer to enzymatic cleavage" (2010). Mechanical Engineering Dissertations. Paper 14. http://hdl.handle.net/2047/d20000984
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