A coarse-grained molecular model for glycosaminoglycans: application to chondroitin, chondroitin sulfate, and hyaluronic acid

Biophys J. 2005 Jun;88(6):3870-87. doi: 10.1529/biophysj.104.058800. Epub 2005 Apr 1.

Abstract

A coarse-grained molecular model is presented for the study of the equilibrium conformation and titration behavior of chondroitin (CH), chondroitin sulfate (CS), and hyaluronic acid (HA)-glycosaminoglycans (GAGs) that play a central role in determining the structure and biomechanical properties of the extracellular matrix of articular cartilage. Systematic coarse-graining from an all-atom description of the disaccharide building blocks retains the polyelectrolytes' specific chemical properties while enabling the simulation of high molecular weight chains that are inaccessible to all-atom representations. Results are presented for the characteristic ratio, the ionic strength-dependent persistence length, the pH-dependent expansion factor for the end-to-end distance, and the titration behavior of the GAGs. Although 4-sulfation of the N-acetyl-D-galactosamine residue is found to increase significantly the intrinsic stiffness of CH with respect to 6-sulfation, only small differences in the titration behavior of the two sulfated forms of CH are found. Persistence length expressions are presented for each type of GAG using a macroscopic (wormlike chain-based) and a microscopic (bond vector correlation-based) definition. Model predictions agree quantitatively with experimental conformation and titration measurements, which support use of the model in the investigation of equilibrium solution properties of GAGs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biophysical Phenomena
  • Biophysics
  • Carbohydrate Conformation
  • Cartilage, Articular / chemistry
  • Chondroitin / chemistry
  • Chondroitin Sulfates / chemistry
  • Disaccharides / chemistry
  • Glycosaminoglycans / chemistry*
  • Hyaluronic Acid / chemistry
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Models, Molecular
  • Molecular Conformation
  • Static Electricity
  • Thermodynamics

Substances

  • Disaccharides
  • Glycosaminoglycans
  • Hyaluronic Acid
  • Chondroitin
  • Chondroitin Sulfates