A coarse-grained molecular model for glycosaminoglycans: application to chondroitin, chondroitin sulfate, and hyaluronic acid.
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.
Bathe
Mark
M
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, 02139, USA.
Rutledge
Gregory C
GC
Grodzinsky
Alan J
AJ
Tidor
Bruce
B
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
D004187:Disaccharides; D006025:Glycosaminoglycans; D006820:Hyaluronic Acid; D002807:Chondroitin; D002809:Chondroitin Sulfates