title: Aggrecan nanoscale solid-fluid interactions are a primary determinant of cartilage dynamic mechanical properties.
abstract: Poroelastic interactions between interstitial fluid and the extracellular matrix of connective tissues are critical to biological and pathophysiological functions involving solute transport, energy dissipation, self-stiffening and lubrication. However, the molecular origins of poroelasticity at the nanoscale are largely unknown. Here, the broad-spectrum dynamic nanomechanical behavior of cartilage aggrecan monolayer is revealed for the first time, including the equilibrium and instantaneous moduli and the peak in the phase angle of the complex modulus. By performing a length scale study and comparing the experimental results to theoretical predictions, we confirm that the mechanism underlying the observed dynamic nanomechanics is due to solid-fluid interactions (poroelasticity) at the molecular scale. Utilizing finite element modeling, the molecular-scale hydraulic permeability of the aggrecan assembly was quantified (kaggrecan = (4.8 ± 2.8) × 10(-15) m(4)/N·s) and found to be similar to the nanoscale hydraulic permeability of intact normal cartilage tissue but much lower than that of early diseased tissue. The mechanisms underlying aggrecan poroelasticity were further investigated by altering electrostatic interactions between the molecule's constituent glycosaminoglycan chains: electrostatic interactions dominated steric interactions in governing molecular behavior. While the hydraulic permeability of aggrecan layers does not change across species and age, aggrecan from adult human cartilage is stiffer than the aggrecan from newborn human tissue.
authors.affiliation: †Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
authors.forename: Hadi Tavakoli
authors.initials: HT
authors.lastname: Nia
authors.affiliation: ‡School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Lin
authors.initials: L
authors.lastname: Han
authors.affiliation: †Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
authors.forename: Iman Soltani
authors.initials: IS
authors.lastname: Bozchalooi
authors.affiliation: §Shriners Hospital for Children, Montreal, Quebec H3G 1A6, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Roughley
authors.affiliation: †Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
authors.forename: Kamal
authors.initials: K
authors.lastname: Youcef-Toumi
authors.affiliation: †Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.|∥Department of Electrical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.|⊥Department of Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Grodzinsky
authors.affiliation: #Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
authors.forename: Christine
authors.initials: C
authors.lastname: Ortiz
mesh_terms: D000328:Adult; D053674:Aggrecans / Q000737:chemistry / Q000378:metabolism*; D001696:Biomechanical Phenomena; D040761:Biomimetic Materials / Q000737:chemistry / Q000378:metabolism*; D002356:Cartilage / Q000737:chemistry / Q000378:metabolism*; D004548:Elasticity; D020342:Finite Element Analysis; D006801:Humans; D007231:Infant, Newborn; D055595:Mechanical Phenomena; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D036103:Nanotechnology; D010539:Permeability; D016062:Porosity; D011487:Protein Conformation; D012212:Rheology; D055672:Static Electricity; D014867:Water / Q000737:chemistry
chemical_list: D053674:Aggrecans; D014867:Water
keywords: AFM; aggrecan; cartilage; dynamic loading; hydraulic permeability; nanomechanics; poroelasticity