Effect on the mechanical properties of type I collagen of intra-molecular lysine-arginine derived advanced glycation end-product cross-linking

J Biomech. 2018 Jan 23:67:55-61. doi: 10.1016/j.jbiomech.2017.11.021. Epub 2017 Nov 28.

Abstract

Non-enzymatic advanced glycation end product (AGE) cross-linking of collagen molecules has been hypothesised to result in significant changes to the mechanical properties of the connective tissues within the body, potentially resulting in a number of age related diseases. We have investigated the effect of two of these cross-links, glucosepane and DOGDIC, on the tensile and lateral moduli of the collagen molecule through the use of a steered molecular dynamics approach, using previously identified preferential formation sites for intra-molecular cross-links. Our results show that the presence of intra-molecular AGE cross-links increases the tensile and lateral Young's moduli in the low strain domain by between 3.0-8.5% and 2.9-60.3% respectively, with little effect exhibited at higher strains.

Keywords: Ageing; Collagen; Glycation; Molecular biomechanics; Molecular dynamics; Protein cross-linking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / chemistry
  • Collagen / chemistry
  • Collagen Type I / chemistry*
  • Connective Tissue / physiology
  • Cross-Linking Reagents / chemistry*
  • Dipeptides
  • Elasticity
  • Glycation End Products, Advanced / chemistry*
  • Humans
  • Hydrogen Bonding
  • Imidazoles / chemistry
  • Lysine / analogs & derivatives
  • Lysine / chemistry
  • Molecular Dynamics Simulation
  • Peptides / chemistry
  • Protein Domains
  • Tensile Strength

Substances

  • Collagen Type I
  • Cross-Linking Reagents
  • Dipeptides
  • Glycation End Products, Advanced
  • Imidazoles
  • N(6)-(2-((4-ammonio-5-oxido-5-oxopentyl)amino)-5-(2,3,4-trihydroxybutyl)3,5-dihydro-4H-imidazol-4-ylidene)lysinate
  • Peptides
  • arginyllysine
  • glucosepane
  • Collagen
  • Arginine
  • Lysine