title: Gel-like behavior in aggrecan assemblies.
abstract: Aggrecan, a large biological polyelectrolyte molecule with a bottlebrush shape, forms complexes with hyaluronic acid (HA) that provide compressive resistance in cartilage. In solutions of aggrecan alone, the concentration dependence of the osmotic pressure Pi is marked by self-assembly of the molecules into aggregates. When HA is added to the solution at low aggrecan concentration c, the osmotic pressure is reduced, but in the physiological concentration range this trend is reversed. The osmotic modulus c partial differentialPi partial differentialc, which determines load bearing resistance, is enhanced in the HA-containing solutions. Dynamic light scattering (DLS) measurements show that the aggregates behave like microgels and that they become denser as the aggrecan concentration increases. The degree of densification is greatest at large distance scales in the microgels, but decreases at short distance scales. Measurements at higher resolution, involving small angle neutron scattering and small angle x-ray scattering (SAXS), confirm that at length scales shorter than 1000 angstroms, the density is independent of the concentration and that the individual bottlebrushes in the microgels retain their identity. The absence of collective diffusion modes in the relaxation spectrum, measured by DLS and neutron spin echo, corroborates the lack of interpenetration among the aggrecan subunits in the microgel. Complexation with HA modifies the long-range spatial organization of the microgels. Comparison of the scattering pattern of the individual aggrecan molecules obtained from SAXS measurements with that of the complexes measured by DLS shows that the aggrecan-HA structure is denser and is more uniform than the random microgels. This enhanced space-filling property allows higher packing densities to be attained, thus, optimizing resistance to osmotic compression.
authors.affiliation: Section on Tissue Biophysics and Biomimetics, Laboratory of Integrative and Medical Biophysics, NICHD, National Institutes of Health, 13 South Drive, Bethesda, Maryland 20892, USA. horkay@helix.nih.gov
authors.forename: Ferenc
authors.initials: F
authors.lastname: Horkay
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Basser
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Hecht
authors.forename: Erik
authors.initials: E
authors.lastname: Geissler
mesh_terms: D053674:Aggrecans / Q000737:chemistry* / Q000648:ultrastructure*; D003198:Computer Simulation; D005782:Gels / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000648:ultrastructure*; D011487:Protein Conformation
chemical_list: D053674:Aggrecans; D005782:Gels; D046912:Multiprotein Complexes