High-bandwidth AFM-based rheology is a sensitive indicator of early cartilage aggrecan degradation relevant to mouse models of osteoarthritis
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Ortiz_High-bandwidth.pdf
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Author(s)
Gauci, Stephanie J.
Frank, Eliot
Fosang, Amanda J.
Ortiz, Christine
Grodzinsky, Alan J.
Tavakoli Nia, Hadi
Azadi Sohi, Mojtaba
Hung, Han-Hwa K.
Date Issued
November 2014
Journal
Journal of Biomechanics
Publisher
Elsevier
Citation
Nia, Hadi T., Stephanie J. Gauci, Mojtaba Azadi, Han-Hwa Hung, Eliot Frank, Amanda J. Fosang, Christine Ortiz, and Alan J. Grodzinsky. “High-Bandwidth AFM-Based Rheology Is a Sensitive Indicator of Early Cartilage Aggrecan Degradation Relevant to Mouse Models of Osteoarthritis.” Journal of Biomechanics 48, no. 1 (January 2015): 162–165.
Version
Author's final manuscript
Abstract
Murine models of osteoarthritis (OA) and post-traumatic OA have been widely used to study the development and progression of these diseases using genetically engineered mouse strains along with surgical or biochemical interventions. However, due to the small size and thickness of murine cartilage, the relationship between mechanical properties, molecular structure and cartilage composition has not been well studied. We adapted a recently developed AFM-based nano-rheology system to probe the dynamic nanomechanical properties of murine cartilage over a wide frequency range of 1 Hz to 10 kHz, and studied the role of glycosaminoglycan (GAG) on the dynamic modulus and poroelastic properties of murine femoral cartilage. We showed that poroelastic properties, highlighting fluid–solid interactions, are more sensitive indicators of loss of mechanical function compared to equilibrium properties in which fluid flow is negligible. These fluid-flow-dependent properties include the hydraulic permeability (an indicator of the resistance of matrix to fluid flow) and the high frequency modulus, obtained at high rates of loading relevant to jumping and impact injury in vivo. Utilizing a fibril-reinforced finite element model, we estimated the poroelastic properties of mouse cartilage over a wide range of loading rates for the first time, and show that the hydraulic permeability increased by a factor ~16 from k[subscript normal] = 7.80 × 10[superscript −16] ± 1.3 × 10[superscript −16] m[superscript 4]/N s to k[subscript GAG-depleted] = 1.26 × 10[superscript −14] ± 6.73 × 10[superscript −15] m[superscript 4]/N s after GAG depletion. The high-frequency modulus, which is related to fluid pressurization and the fibrillar network, decreased significantly after GAG depletion. In contrast, the equilibrium modulus, which is fluid-flow independent, did not show a statistically significant alteration following GAG depletion.
MIT Department
Massachusetts Institute of Technology. Center for Biomedical Engineering
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.jbiomech.2014.11.012
