A Coarse-Grained Molecular Model for Glycosaminoglycans: Application to Chondroitin, Chondroitin Sulfate, and Hyaluronic Acid

• Published in: Biophysical journal Vol. 88; no. 6; pp. 3870 - 3887
• Main Authors: Bathe, Mark, Rutledge, Gregory C., Grodzinsky, Alan J., Tidor, Bruce
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2005; Biophysical Society
• Subjects: Acids; Biophysical Phenomena; Biophysical Theory and Modeling; Biophysics; Carbohydrate Conformation; Cartilage, Articular - chemistry; Cells; Chondroitin - chemistry; Chondroitin Sulfates - chemistry; Disaccharides - chemistry; Glycosaminoglycans - chemistry; Grain; Hyaluronic Acid - chemistry; Hydrogen-Ion Concentration; In Vitro Techniques; Models, Molecular; Molecular Conformation; Static Electricity; Sugar; Thermodynamics; Topology
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1529/biophysj.104.058800

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.