Targeted Analysis of the Size Distribution of Heavy Chain-Modified Hyaluronan with Solid-State Nanopores

The glycosaminoglycan hyaluronan (HA) plays important roles in diverse physiological functions where the distribution of its molecular weight (MW) can influence its behavior and is known to change in response to disease conditions. During inflammation, HA undergoes a covalent modification in which h...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 2024-01, Vol.96 (4), p.1606-1613
Main Authors: Erxleben, Dorothea A., Dodd, Rebecca J., Day, Anthony J., Green, Dixy E., DeAngelis, Paul L., Poddar, Suruchi, Enghild, Jan J., Huebner, Janet L., Kraus, Virginia B., Watkins, Amanda R., Reesink, Heidi L., Rahbar, Elaheh, Hall, Adam R.
Format: Article
Language:English
Subjects:
Glycosaminoglycans
Hyaluronic acid
Molecular weight
Molecular weight distribution
Size distribution
Solid state
Synovial fluid
Synovitis
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Summary:The glycosaminoglycan hyaluronan (HA) plays important roles in diverse physiological functions where the distribution of its molecular weight (MW) can influence its behavior and is known to change in response to disease conditions. During inflammation, HA undergoes a covalent modification in which heavy chain subunits of the inter-alpha-inhibitor family of proteins are transferred to its structure, forming heavy chain-HA (HC•HA) complexes. While limited assessments of HC•HA have been performed previously, determining the size distribution of its HA component remains a challenge. Here, we describe a selective method for extracting HC•HA from mixtures that yields material amenable to MW analysis with a solid-state nanopore sensor. After demonstrating the approach in vitro, we validate extraction of HC•HA from osteoarthritic human synovial fluid as a model complex biological matrix. Finally, we apply our technique to pathophysiology by measuring the size distributions of HC•HA and total HA in an equine model of synovitis.
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.3c04387