Cartilage Aggrecan Can Undergo Self-Adhesion

Here it is reported that aggrecan, the highly negatively charged macromolecule in the cartilage extracellular matrix, undergoes Ca2+-mediated self-adhesion after static compression even in the presence of strong electrostatic repulsion in physiological-like solution conditions. Aggrecan was chemically end-attached onto gold-coated planar silicon substrates and gold-coated microspherical atomic force microscope probe tips (end radius R ≈ 2.5 μm) at a density (∼40 mg/mL) that simulates physiological conditions in the tissue (∼20–80 mg/mL). Colloidal force spectroscopy was employed to measure the adhesion between opposing aggrecan monolayers in NaCl (0.001–1.0 M) and NaCl + CaCl2 ([Cl−] = 0.15 M, [Ca2+] = 0 – 75 mM) aqueous electrolyte solutions. Aggrecan self-adhesion was found to increase with increasing surface equilibration time upon compression (0–30 s). Hydrogen bonding and physical entanglements between the chondroitin sulfate-glycosaminoglycan side chains are proposed as important factors contributing to aggrecan self-adhesion. Self-adhesion was found to significantly increase with decreasing bath ionic strength (and hence, electrostatic double-layer repulsion), as well as increasing Ca2+ concentration due to the additional ion-bridging effects. It is hypothesized that aggrecan self-adhesion, and the macromolecular energy dissipation that results from this self-adhesion, could be important factors contributing to the self-assembled architecture and integrity of the cartilage extracellular matrix in vivo.