Hard to beat! -Lessons from hummingbird transthyretin about protein stability in complex flows 

Thursday, 03 September 2026, 11:00

JKU Linz (KG 519)

Authors:

Irina Ritsch, Maria A Martinez-Yamout, Daniel Scholl, Maria Rafiq, Gabriel C Lander, H Jane Dyson, Peter E Wright

Transthyretin (TTR) is a blood serum protein involved in spontaneous and hereditary amyloidosis (ATTR) characterized by the formation and deposition of insoluble amyloid protein fibrils in tissues of patients.1 In vivo, the molecular mechanism by which the stable, natively folded protein tetramer transitions to the fibrillar state remains unclear, but mechanical forces from fluid flow have been proposed as a contributing factor.2 We explored in vitro how fluid flow that is intended to mimic chaotic blood circulation can induce TTR aggregation, by a simple but efficient rapid stirring (agitation) experiment, and used high resolution NMR experiments to investigate effects at the molecular level.3 Exciting mechanistic insight was found when comparing human TTR to natural TTR ortholog variants from ‘high performance’ species that have evolved strongly diverging cardiovascular systems and heart rates (hummingbird with fast heart rate, and African elephant with slow heart rate).4

Literature:

1. Benson, M. D. et al., Transthyretin amyloidosis. Amyloid 3, 44–56 (1996).

2. Hill, E. K., et al., Shear Flow Induces Amyloid Fibril Formation. Biomacromolecules 7, 10–13 (2006).

3. Ritsch, I. et al., Initiation of transthyretin aggregation at neutral pH by fluid agitation, PNAS, 122, 11, (2025).

4. Ritsch, I. et al. From Hummingbird to Elephant: Amyloid Formation in Natural Transthyretin Variants, bioRxiv (2026), doi: 10.64898/2026.07.09.737598.