title: High-bandwidth AFM-based rheology reveals that cartilage is most sensitive to high loading rates at early stages of impairment.
abstract: Utilizing a newly developed atomic-force-microscopy-based wide-frequency rheology system, we measured the dynamic nanomechanical behavior of normal and glycosaminoglycan (GAG)-depleted cartilage, the latter representing matrix degradation that occurs at the earliest stages of osteoarthritis. We observed unique variations in the frequency-dependent stiffness and hydraulic permeability of cartilage in the 1 Hz-to-10 kHz range, a frequency range that is relevant to joint motions from normal ambulation to high-frequency impact loading. Measurement in this frequency range is well beyond the capabilities of typical commercial atomic force microscopes. We showed that the dynamic modulus of cartilage undergoes a dramatic alteration after GAG loss, even with the collagen network still intact: whereas the magnitude of the dynamic modulus decreased two- to threefold at higher frequencies, the peak frequency of the phase angle of the modulus (representing fluid-solid frictional dissipation) increased 15-fold from 55 Hz in normal cartilage to 800 Hz after GAG depletion. These results, based on a fibril-reinforced poroelastic finite-element model, demonstrated that GAG loss caused a dramatic increase in cartilage hydraulic permeability (up to 25-fold), suggesting that early osteoarthritic cartilage is more vulnerable to higher loading rates than to the conventionally studied "loading magnitude". Thus, over the wide frequency range of joint motion during daily activities, hydraulic permeability appears the most sensitive marker of early tissue degradation.
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Hadi Tavakoli
authors.initials: HT
authors.lastname: Nia
authors.forename: Iman S
authors.initials: IS
authors.lastname: Bozchalooi
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Han
authors.forename: Han-Hwa
authors.initials: HH
authors.lastname: Hung
authors.forename: Eliot
authors.initials: E
authors.lastname: Frank
authors.forename: Kamal
authors.initials: K
authors.lastname: Youcef-Toumi
authors.forename: Christine
authors.initials: C
authors.lastname: Ortiz
authors.forename: Alan
authors.initials: A
authors.lastname: Grodzinsky
mesh_terms: D001696:Biomechanical Phenomena; D002356:Cartilage / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D008422:Materials Testing; D055595:Mechanical Phenomena; D018625:Microscopy, Atomic Force; D036103:Nanotechnology; D010539:Permeability; D011312:Pressure; D012212:Rheology; D013997:Time Factors; D016474:Weight-Bearing
chemical_list: D006025:Glycosaminoglycans
references.citation: Eur Phys J E Soft Matter. 2002 Dec;9(5):435-41
references.pmid: 15011090
references.citation: Nat Nanotechnol. 2009 Mar;4(3):186-92
references.pmid: 19265849
references.citation: J Struct Biol. 2003 Sep;143(3):242-57
references.pmid: 14572479
references.citation: J Bone Joint Surg Br. 1987 Nov;69(5):807-11
references.pmid: 3680348
references.citation: J Biomech. 2008 Aug 7;41(11):2430-7
references.pmid: 18619596
references.citation: Microsc Res Tech. 1994 Aug 1;28(5):385-97
references.pmid: 7919526
references.citation: Arthritis Rheum. 2007 Jan;56(1):188-98
references.pmid: 17195221
references.citation: Biochim Biophys Acta. 1986 Sep 4;883(2):173-7
references.pmid: 3091074
references.citation: J Orthop Res. 2011 Jun;29(6):802-9
references.pmid: 21520254
references.citation: Annu Rev Biomed Eng. 2000;2:691-713
references.pmid: 11701528
references.citation: Proc Natl Acad Sci U S A. 2012 Sep 18;109(38):15101-8
references.pmid: 22932871
references.citation: Biophys J. 2007 Feb 15;92(4):1384-98
references.pmid: 17142289
references.citation: Biophys J. 2011 Apr 6;100(7):1846-54
references.pmid: 21463599
references.citation: Cartilage. 2012 Oct 1;3(4):314-322
references.pmid: 24015324
references.citation: Nature. 2005 May 19;435(7040):365-9
references.pmid: 15902261
references.citation: Osteoarthritis Cartilage. 2012 May;20(5):413-421
references.pmid: 22313971
references.citation: J Biomech Eng. 1999 Jun;121(3):340-7
references.pmid: 10396701
references.citation: Arch Biochem Biophys. 1999 Jun 1;366(1):1-7
references.pmid: 10334856
references.citation: J Bone Joint Surg Br. 1991 Sep;73(5):795-801
references.pmid: 1894669
references.citation: Am J Sports Med. 1996 Sep-Oct;24(5):676-83
references.pmid: 8883692
references.citation: Biorheology. 1975 Jun;12(3-4):233-48
references.pmid: 1106795
references.citation: Biophys J. 2011 Nov 2;101(9):2304-13
references.pmid: 22067171
references.citation: Arthritis Rheum. 1995 Feb;38(2):173-83
references.pmid: 7848307
references.citation: J Orthop Res. 2001 Nov;19(6):1113-21
references.pmid: 11781013
references.citation: J Biomech. 1987;20(6):629-39
references.pmid: 3611138
references.citation: Arthritis Rheum. 2000 Mar;43(3):664-72
references.pmid: 10728761
references.citation: J Biomech Eng. 1980 Feb;102(1):73-84
references.pmid: 7382457
references.citation: Arthritis Rheum. 2007 May;56(5):1549-58
references.pmid: 17469134
references.citation: J Orthop Res. 1985;3(2):148-59
references.pmid: 3998893
references.citation: J Biomech. 1985;18(6):415-22
references.pmid: 4030798
references.citation: J Biomech. 1998 Oct;31(10):927-34
references.pmid: 9840758
references.citation: J Biomech. 1987;20(7):703-14
references.pmid: 3654668
references.citation: J Magn Reson Imaging. 2008 Jul;28(1):151-7
references.pmid: 18581328
references.citation: J Orthop Res. 1994 Jul;12(4):474-84
references.pmid: 8064478
references.citation: J Biomech. 1995 Sep;28(9):1055-66
references.pmid: 7559675
references.citation: Arthritis Rheum. 2009 Oct;60(10):2985-96
references.pmid: 19790045
references.citation: J Biomech. 2006;39(14):2555-65
references.pmid: 16289077
references.citation: J Biomech. 2007;40(1):182-90
references.pmid: 16387310
references.citation: J Biomech. 1987;20(6):615-27
references.pmid: 3611137
references.citation: Exp Mech. 2009;49(2):235-246
references.pmid: 20300451
references.citation: J Biomech. 2010 Feb 10;43(3):469-76
references.pmid: 19889416
references.citation: Biophys J. 2004 Mar;86(3):1777-93
references.pmid: 14990504