Dataset Information

Effect of collagenase-gelatinase ratio on the mechanical properties of a collagen fibril: a combined Monte Carlo-molecular dynamics study.

ABSTRACT: 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.

SUBMITTER: Powell B

PROVIDER: S-EPMC6825035 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of collagenase-gelatinase ratio on the mechanical properties of a collagen fibril: a combined Monte Carlo-molecular dynamics study.

Powell Bethany B Malaspina David C DC Szleifer Igal I Dhaher Yasin Y

Biomechanics and modeling in mechanobiology 20190603 6

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 ...[more]

PMID: 31161353

Similar Datasets

Project description:To penetrate host tissues, histotoxic clostridia secrete virulence factors including enzymes to hydrolyze extracellular matrix. Clostridium histolyticum, recently renamed as Hathewaya histolytica, produces two classes of collagenase (ColG and ColH). The high-speed AFM study showed that ColG collagenase moves unidirectionally to plane collagen fibril and rebundles fibril when stalled . The structural explanation of the roles for the tandem collagen-binding segment (CBDs) is illuminated by its calcium-bound crystal structure at 1.9 Å resolution (Rwork = 15.0%; Rfree = 19.6%). Activation may involve calcium-dependent domain rearrangement supported by both small-angle X-ray scattering and size exclusion chromatography. At pCa ? 5 (pCa = -log[Ca2+ ]), the tandem CBD adopts an extended conformation that may facilitate secretion from the bacterium. At pCa ? 4, the compact structure seen in the crystal structure is adopted. This arrangement positions the two binding surfaces ~ 55 Å apart, and possibly ushers ColG along tropocollagen molecules that allow for unidirectional movement. A sequential binding mode where tighter binding CBD2 binds first could aid in processivity as well. Switch from processive collagenolysis to fibril rearrangement could be concentration dependent. Collagen fibril formation is retarded at 1 : 1 molar ratio of tandem CBD to collagen. Tandem CBD may help isolate a tropocollagen molecule from a fibril at this ratio. At 0.1 : 1 to 0.5 : 1 molar ratios fibril self-assembly was accelerated. Gain of function as a result of gene duplication of CBD for the M9B enzymes is speculated. The binding and activation modes described here will aid in drug delivery design. ACCESSION CODES:The full atomic coordinates of the tandem CBD and its corresponding structure factor amplitudes have been deposited in the Protein Data Bank (PDB accession code 5IKU). Small-angle X-ray scattering data and corresponding ab initio models have been submitted to the Small Angle Scattering Biological Data Bank (SASBDB). Accession codes CL2, collagenase module 2, CN2, CP2 are assigned to envelopes for tandem CBD at -log[Ca2+ ] (pCa) 3, 4, 5, and 6, respectively. Accession code DC64 was assigned to the complex of polycystic kidney disease-CBD1-CBD2 with mini-collagen.

Dataset Information

Effect of collagenase-gelatinase ratio on the mechanical properties of a collagen fibril: a combined Monte Carlo-molecular dynamics study.

Publications

Effect of collagenase-gelatinase ratio on the mechanical properties of a collagen fibril: a combined Monte Carlo-molecular dynamics study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets