title: A coarse-grained molecular model for glycosaminoglycans: application to chondroitin, chondroitin sulfate, and hyaluronic acid.
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.
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, 02139, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Bathe
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Rutledge
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Grodzinsky
authors.forename: Bruce
authors.initials: B
authors.lastname: Tidor
mesh_terms: D055592:Biophysical Phenomena; D001703:Biophysics; D002236:Carbohydrate Conformation; D002358:Cartilage, Articular / Q000737:chemistry; D002807:Chondroitin / Q000737:chemistry; D002809:Chondroitin Sulfates / Q000737:chemistry; D004187:Disaccharides / Q000737:chemistry; D006025:Glycosaminoglycans / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008958:Models, Molecular; D008968:Molecular Conformation; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D004187:Disaccharides; D006025:Glycosaminoglycans; D006820:Hyaluronic Acid; D002807:Chondroitin; D002809:Chondroitin Sulfates