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bioRxiv · 10.64898/2026.08.27.747546

Thermodynamic properties and stability of HMGB1 complexes with linear polyelectrolytes elucidated by nano differential scanning fluorimetry

Watson, J.·Klumpp, A.·Kagelmacher, M.·Moon, E.·Traviankina, M.·Krage, C.·Pigaleva, M.
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Abstract

The High Mobility Group Box 1 (HMGB1) protein performs multiple essential functions in the body, ranging from DNA regulation to the activation and mediation of immune responses. However, HMGB1 has been also implicated in several pathological conditions, such as rheumatoid arthritis, sepsis, autoimmune diseases, tumors, and Alzheimer's disease. As a result, HMGB1 is of increasing interest as a therapeutic target. Binding to heparin has been reported to inhibit HMGB1's pathological activity during sepsis in clinical settings. In this work, we compare the interactions of HMGB1 with heparin and its' synthetic analog linear polyglycerol sulfate (lPGS) from the viewpoint of stability and changes to association behavior. This analysis focuses on thermal stability, secondary-structure changes, and particle-size evolution using nano-differential scanning fluorimetry (nanoDSF), circular dichroism spectroscopy (CD), and dynamic light scattering (DLS).

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Watson, J., Klumpp, A., Kagelmacher, M., Moon, E., Traviankina, M., Krage, C., Pigaleva, M.. 2026-08-28. Thermodynamic properties and stability of HMGB1 complexes with linear polyelectrolytes elucidated by nano differential scanning fluorimetry. https://doi.org/10.64898/2026.08.27.747546

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