Osmotic pressure characterization of glycosaminoglycans using full-atomistic molecular models

The osmotic pressure of chondroitin sulfate glycosaminoglycans (CS-GAGs) in a simulated physiological environment of articular cartilage is thoroughly examined in silico using full atomistic models. The effects of chemical and physical properties were investigated to elucidate the molecular origins of cartilage biomechanical behavior providing singleatomistic resolution analyses which would not be attainable with in vivo or in in vitro techniques. CS-GAG chains exhibit plastic deformation behavior under compressive load in the extracellular matrix (ECM) and osmotic pressure is the main contributor in balancing external pressures. This study focuses on quantitatively expressing this contribution. Molecular dynamics was used to imitate the physiological environment experienced by GAGs inside articular cartilage by simulating a semipermeable membrane acting on the full atomistic chains during compression. To this end, a variety of validation techniques, pre-simulation tasks, and comparisons were conducted to validate the test methodology. CS-GAGs with varying lengths and sulfation positions underwent simulation under varying molar concentrations. Sulfation positioning is found to have negligible influence on GAG osmotic pressure behavior; attributed to the small distance between the position of 4and 6sulfation relative to the intermolecular spacing between the CS chains. However, differences between sulfated and unsulfated chains did have a significant influence on osmotic pressure. Length of disaccharides was also found to have a significant contribution to osmotic pressure. Measurements are comparable to previous coarse grained studies and experimental data.