Skip over navigation

 

Molecular Mechanisms Underlying Cartilage Poroelasticity

Hadi Tavakoli Nia (MIT), Lin Han (), Iman Soltani (), Kamal Youcef-Toumi (), Christine Ortiz (), Alan Grodzinsky ()

Experimental Nanobiomechanics

Mon 9:00 - 10:30

Barus-Holley 163

Aggrecan and type II collagen are the two important macromolecules contributing to the biomechanical properties of cartilage extracellular matrix (ECM). Loss of aggrecan is one of the earliest events in osteoarthritis (OA), a prevalent disease at all ages including young patients suffering from traumatic joint injury. Although the dynamic (rate-dependent) biomechanical functions of cartilage have been studied at the tissue level, including self-stiffening and energy dissipation, the mechanisms underlying these behaviors at the molecular level are not well understood. Utilizing a high-frequency AFM-based nano-rheology system developed recently, we measured the magnitude and phase of the dynamic stiffness of end-grafted aggrecan brush layers (height: 30-300 nm) over the wide frequency of 1 Hz to 10 kHz. We showed experimentally and theoretically that the dominant mechanism underlying the dynamic nanomechanics of aggrecan is poroelasticity, i.e. fluid-solid interactions associated with the glycosaminoglycan (GAG) chains of aggrecan. Using an anisotropic poroelastic model, we estimated the intrinsic material properties of these aggrecan layers, including the axial equilibrium modulus EL and hydraulic permeability k. The close agreement between k estimated for the aggrecan layer and the k previously measured for normal ECM suggests that aggrecan is the major molecular component of cartilage responsible for its poroelastic properties. By measuring EL and k of aggrecan at different ionic strengths and offset strains, we showed that electrostatic GAG-GAG interactions are primarily responsible for determining the pore size and, hence, the poroelasticity of aggrecan, compared to steric interactions between GAG chains. Finally, by estimating EL and k of aggrecans from different species (human vs bovine) and age (newborn vs adult), we showed that the stiffness of aggrecan increased by age, but there was no significant change in the hydraulic permeability across age or species.