Aggrecan: approaches to study biophysical and biomechanical properties

Aggrecan, the most abundant extracellular proteoglycan in cartilage (~35 % by dry weight), plays a key role in the biophysical and biomechanical properties of cartilage. Here, we review several approaches based on atomic force microscopy (AFM) to probe the physical, mechanical, and structural properties of aggrecan at the molecular level. These approaches probe the response of aggrecan over a wide time (frequency) scale, ranging from equilibrium to impact dynamic loading. Experimental and theoretical methods are described for the investigation of electrostatic and fluid-solid interactions that are key mechanisms underlying the biomechanical and physicochemical functions of aggrecan. Using AFM-based imaging and nanoindentation, ultrastructural features of aggrecan are related to its mechanical properties, based on aggrecans harvested from human vs. bovine, immature vs. mature, and healthy vs. osteoarthritic cartilage.