Journal
BIOMECHANICS AND MODELING IN MECHANOBIOLOGY
Volume 18, Issue 6, Pages 1809-1819Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s10237-019-01178-6
Keywords
Collagen fibril; Mechanical properties; Collagenase; Gelatinase; Molecular dynamics; Monte Carlo
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Funding
- National Institute of Biomedical Imaging and Bioengineering (US) [1U01 EB015410-01A1]
- National Institutes of Health [T32 HD07418]
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Loading in cartilage is supported primarily by fibrillar collagen, and damage will impair the function of the tissue, leading to pathologies such as osteoarthritis. Damage is initiated by two types of matrix metalloproteinases, collagenase and gelatinase, that cleave and denature the collagen fibrils in the tissue. Experimental and modeling studies have revealed insights into the individual contributions of these two types of MMPs, as well as the mechanical response of intact fibrils and fibrils that have experienced random surface degradation. However, no research has comprehensively examined the combined influences of collagenases and gelatinases on collagen degradation nor studied the mechanical consequences of biological degradation of collagen fibrils. Such preclinical examinations are required to gain insights into understanding, treating, and preventing degradation-related cartilage pathology. To develop these insights, we use sequential Monte Carlo and molecular dynamics simulations to probe the effect of enzymatic degradation on the structure and mechanics of a single collagen fibril. We find that the mechanical response depends on the ratio of collagenase to gelatinase-not just the amount of lost fibril mass-and we provide a possible mechanism underlying this phenomenon. Overall, by characterizing the combined influences of collagenases and gelatinases on fibril degradation and mechanics at the preclinical research stage, we gain insights that may facilitate the development of targeted interventions to prevent the damage and loss of mechanical integrity that can lead to cartilage pathology.
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