Abstract
Aggrecan, a highly charged macromolecule found in articular cartilage, was investigated in aqueous salt solutions with proton nuclear magnetic resonance. The longitudinal and transverse relaxation rates were determined at two different field strengths, 9.4 T and 0.5 T, for a range of temperatures and aggrecan concentrations. The diffusion coefficients of the water molecules were also measured as a function of temperature and aggrecan concentration, using a pulsed field gradient technique at 9.4 T. Assuming an Arrhenius relationship, the activation energies for the various relaxation processes and the translational motion of the water molecules were determined from temperature dependencies as a function of aggrecan concentration in the range 0–5.3% w/w. The longitudinal relaxation rate and inverse diffusion coefficient were approximately equally dependent on concentration and only increased by upto 20% from that of the salt solution. The transverse relaxation rate at high field demonstrated greatest concentration dependence, changing by an order of magnitude across the concentration range examined. We attribute this primarily to chemical exchange. Activation energies appeared to be approximately independent of aggrecan concentration, except for that of the low-field transverse relaxation rate, which decreased with concentration.
Highlights
Aggrecan is the main proteoglycan found in cartilage [1]
There are some clear differences between the four graphs in figure 1; for both field strengths, especially at the higher field, the transverse relaxation rate R2 is more sensitive to the presence of aggrecan than the longitudinal rate R1
This feature is consistent across many independent measurements and we suggest that this represents a sensitivity in the relaxation rates to a general change in aggrecan-assembly structure, such as self-assembly [3]
Summary
The macromolecule tends to be polydisperse with an average molecular weight of approximately 2.5 MDa [2]. It has a core protein of approximately 300 kDa [3] and has of the order of 100 attached glycosaminoglycan (GAG) side chains, of which. The GAG chains are linear polymers of approximately 30 disaccharide monomers with each disaccharide containing carboxylate and sulfate groups which are negatively charged under physiological pH conditions. Each disaccharide is doubly negatively charged and the highly charged GAG chains give the aggrecan molecule an extended, semi-rigid bottlebrush conformation in solution [3]
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