The role of lubricin in the mechanical behavior of synovial fluid

doi:10.1073/pnas.0608558104

The role of lubricin in the mechanical behavior of synovial fluid

^†Division of Engineering and
^‡Department of Emergency Medicine, Brown University, Providence, RI 02912; and
^¶Department of Genetics and Center for Human Genetics, Case School of Medicine and University Hospitals of Cleveland, Cleveland, OH 44106

Edited by Robert Langer, Massachusetts Institute of Technology, Cambridge, MA, and approved February 28, 2007 (received for review September 28, 2006)

Abstract

Synovial fluid is a semidilute hyaluronate (HA) polymer solution, the rheology of which depends on HA–protein interactions, and lubricin is a HA-binding protein found in synovial fluid and at cartilage surfaces, where it contributes to boundary lubrication under load. Individuals with genetic deficiency of lubricin develop precocious joint failure. The role of lubricin in synovial fluid rheology is not known. We used a multiple-particle-tracking microrheology technique to study the molecular interactions between lubricin and HA in synovial fluid. Particles (200 nm mean diameter) embedded in normal and lubricin-deficient synovial fluid samples were tracked separately by using multiple-particle-tracking microrheology. The time-dependent ensemble-averaged mean-squared displacements of all of the particles were measured over a range of physiologically relevant frequencies. The mean-squared displacement correlation with time lag had slopes with values of unity for simple HA solutions and for synovial fluid from an individual who genetically lacked lubricin, in contrast to slopes with values less than unity (α ≈ 0.6) for normal synovial fluid. These data correlated with bulk rheology studies of the same samples. We found that the subdiffusive and elastic behavior of synovial fluid, at physiological shear rates, was absent in fluid from a patient who lacks lubricin. We conclude that lubricin provides synovial fluid with an ability to dissipate strain energy induced by mammalian locomotion, which is a chondroprotective feature that is distinct from boundary lubrication.

Footnotes

^§To whom correspondence should be addressed at: Department of Emergency Medicine, Rhode Island Hospital, Coro West Building, 1 Hoppin Street, Providence, RI 02903. E-mail: gjay{at}lifespan.org
Author contributions: G.D.J., J.R.T., and K.S.B. designed research; M.L.W. and M.C.L. contributed new reagents/analytic tools; G.D.J., J.R.T., and K.S.B. analyzed data; and G.D.J., J.R.T., M.L.W., and K.S.B. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
↵ ‖ Jay, G. D., Carpten, J. D., Rhee, D. K., Torres, J. R., Marcelino, J., Warman, M. L., Transactions of the Annual Meeting of the Orthopedic Research Society, Feb. 3, 2003, New Orleans, LA, p. 134 (abstr.).
Abbreviations:

HA,

hyaluronate;

BSF,

bovine synovial fluid;

MPTM,

multiple-particle-tracking microrheology;

CACP,

camptodactyly-arthropathy-coxa vara-pericarditis;

hSF,

human synovial fluid;

MSD,

ensemble-averaged mean-squared displacement;

RMSD,

root MSD;

ET-BSF,

enzyme-treated BSF;

PDF,

probability density function;

UHA,

human umbilical cord HA.