Molecular Interactions between Collagen and Aggrecan from the Cartilage Extracellular Matrix

In this study, colloidal force spectroscopy was utilized to quantify interactions between collagen and aggrecan in physiological and non-physiological aqueous solutions. An aggrecanfunctionalized probe tip (R ~ 2.5μm) was indented ~500nm into the surface of a native collagen network, composed of trypsin-treated, proteoglycan-depleted cartilage. The resulting forceindentation curves were used to calculate the adhesion force and adhesion energy of the molecular interaction. Heterogeneous long-range adhesion was observed up to ~ 2.5 μm extension upon retraction after compressing the tip into the sample for a given surface dwell time, t. The adhesion force showed an asymptotic nonlinear increase with t, reaching a maximum value of 3.1 ± 0.2 nN at t = 60 s. Aggrecan-collagen interactions displayed a dependence on ionic strength, with a maximum adhesion force of 4.3 ± 0.3 nN at 1.0 M NaCl (t = 30 s). In addition, aggrecan-collagen interactions showed [Ca]-dependence with a maximum adhesion force of 7.4 ± 0.3 nN with a [Ca] = 20 mM (t = 30 s, 0.15 M). Molecular interactions between aggrecan and collagen are important in determining structural integrity of the cartilage extracellular matrix and its biological functions, such as energy dissipation, osmotic swelling and hydraulic permeability. Thesis Supervisor: Christine Ortiz Title: Professor of Materials Science and Engineering Thesis Supervisor: Alan J. Grodzinsky Title: Professor of Biological, Electrical and Mechanical Engineering