Heat of supersaturation-limited amyloid burst directly monitored by isothermal titration calorimetry

Significance Although amyloid fibrils are associated with numerous pathologies, their conformational stability remains largely unknown. In particular, calorimetry, one of the most powerful methods used to study the thermodynamic properties of globular proteins, has not played a significant role in understanding protein aggregation. Here, with β 2 -microglobulin, we established direct heat measurements of supersaturation-limited amyloid fibrillation using an isothermal titration calorimeter. We also revealed the thermodynamics of amorphous aggregation. By creating a totally new field of calorimetric study of protein misfolding, we can now comprehensively address the thermodynamics of protein folding and misfolding.