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Honey, U.

Publications and source records attributed to Honey, U..

2 recordsLinked to original sources

Functional Differentiation of Type II and Type I Collagen Articular Models in Synovial Fluid Film Formation and Recombinant Lubricin Retention

Collagen type II (Col-II) and collagen type I (Col-I) are major components of articular cartilage present at different ratios at its surface. Understanding how each of these components mediates the assembly of molecular films derived from synovial fluid (SF), the native lubricant of synovial joints, is critical to explain the loss of mechanical performance in pathological conditions, guide the design of biomaterial implants meant to be in contact with SF, and develop molecular therapies to restore SF properties. This work demonstrates that Col-II articular surface model assists in scaffolding of full SF-derived films, while Col-I model lacks SF film scaffolding capabilities. However, when Col-II and Col-I are exposed to recombinant lubricin (rLub) alone, the major boundary lubricant in SF, both adsorbed and retained similar amounts. These insights, deduced from quartz crystal microbalance with dissipation, diffuse reflectance circular dichroism, and atomic force microscopy, reveal possible mechanisms underlying the loss of mechanical performance of synovial joints in pathology, where Col-I becomes the major collagenous component of the articular cartilage surface, as well as considerations for designing functional biomaterial implants. Furthermore, this work reinforces the idea of rLub as an intra-articular osteoarthritis therapy with the ability to bind to Col-II and Col-I, irrespectively. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=170 SRC="FIGDIR/small/726594v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@138a77borg.highwire.dtl.DTLVardef@7b8512org.highwire.dtl.DTLVardef@15d7060org.highwire.dtl.DTLVardef@17ccf20_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

Surface-immobilized fibronectin conformation drives synovial fluid adsorption and film formation

The articular cartilage extracellular matrix (ECM) is a complex network of biomolecules that includes fibronectin (FN). FN acts as an extracellular glue, controlling the assembly of other macromolecular constituents to the ECM. However, how FN participates in the binding and retention of synovial fluid components, the natural lubricant of articulated joints, to form a wear-protecting and lubricating film has not been established. This study reports on the role of FN and its molecular conformation in mediating macromolecular assembly of synovial fluid ad-layers. FN films as precursor films on functionalized surfaces, a model of FNs articular cartilage surface, adsorbed and retained different amounts of synovial fluid (SF) depending on FN conformation. FN conformational changes were induced by depositing FN from bulk solution at pH 7 (extended state) or at pH 4 (unfolded state) on self-assembled monolayers on gold-coated quartz crystals, followed by adsorption of diluted SF (25%) onto FN precursor films. Mass density, thin film compliance, surface morphologies, and the secondary and tertiary structures of adsorbed FN films reveal pH-induced differences. FN films deposited at pH 4 were thicker, more rigid, showed a more homogeneous morphology, and had altered -helix and {beta}-sheet content, compared to FN films deposited at pH 7. FN precursor films deposited at pH 7 adsorbed and retained more synovial fluid than those at pH 4, revealing the importance of FN conformation at the articular cartilage surface to bind and maintain a thin layer of synovial fluid constituents. This knowledge will enable a better understanding of the molecular interactions and synergies between the articular cartilage ECM components and SF. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=198 SRC="FIGDIR/small/650860v2_ufig1.gif" ALT="Figure 1"> View larger version (75K): org.highwire.dtl.DTLVardef@871413org.highwire.dtl.DTLVardef@3712a5org.highwire.dtl.DTLVardef@1a92b78org.highwire.dtl.DTLVardef@164e79f_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗