2024/08/09 by Pushpa Rampratap, Alessia Lasorsa, Abinaya Arunachalam +3 · 1 voice · 1 citation
Chemistry · Biochemistry, Genetics and Molecular Biology · Medicine · #Advanced NMR Techniques and Applications #Proteoglycans and glycosaminoglycans research #Advanced MRI Techniques and Applications
paper · pdf · doi:10.1021/acsami.4c08428
openalex publication_date 2024/08/09 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/23
High Resolution Image Download MS PowerPoint Slide High-molecular-weight (HMW) hyaluronic acid (HA) is a highly abundant natural polysaccharide and a fundamental component of the extracellular matrix (ECM). Its size and concentration regulate tissues’ macro- and microenvironments, and its upregulation is a hallmark feature of certain tumors. Yet, the conformational dynamics of HMW-HA and how it engages with the components of the ECM microenvironment remain poorly understood at the molecular level. Probing the molecular structure and dynamics of HMW polysaccharides in a hydrated, physiological-like environment is crucial and also technically challenging. Here, we deploy advanced magic-angle spinning (MAS) solid-state NMR spectroscopy in combination with isotopic enrichment to enable an in-depth study of HMW-HA to address this challenge. This approach resolves multiple coexisting HA conformations and dynamics as a function of environmental conditions. By combining 13 C-labeled HA with unlabeled ECM components, we detect by MAS NMR HA-specific changes in global and local conformational dynamics as a consequence of hydration and ECM interactions. These measurements reveal atom-specific variations in the dynamics and structure of the N -acetylglucosamine moiety of HA. We discuss possible implications for interactions that stabilize the structure of HMW-HA and facilitate its recognition by HA-binding proteins. The described methods apply similarly to the studies of the molecular structure and dynamics of HA in tumor contexts and in other biological tissues as well as HMW-HA hydrogels and nanoparticles used for biomedical and/or pharmaceutical applications.