Study on the thermodynamics and regulation of amyloid formation using calorimetry

为了研究蛋白质错误折叠诱导聚集的热力学并建立一种新的分析方法，采用等温滴定量热法（ITC）对几种淀粉样蛋白和多肽的淀粉样形成进行了研究。我揭示了淀粉样蛋白的形成在滞后时间后会产生放热，并使用内部算法获得了热力学参数，如焓变。我进一步挑战阐明淀粉样蛋白形成的动力学性质，并可以计算淀粉样蛋白纤颤成核和延伸的速率常数。利用这些参数构建的能量格局揭示了b2m的多态淀粉样蛋白形成。基于itc的分析为研究蛋白质聚集的热力学、动力学和机制提供了一种强有力的方法。

In order to study thermodynamics of protein misfolding-induced aggregation and establish a new assay, isothermal titration calorimetry (ITC) was performed on amyloidogenesis of several amyloidogenic proteins and peptides. I revealed that amyloid formation resulited in exothermic heat after the lag time, and obtained thermodynamic parameters such as the change in enthalpy using in-house algorithms. I further challenged to elucidate the kinetic property of amyloid formation, and could calculate the rate constant of nucleation and elongation of amyloid fibrillation. Energy landscape built using these parameters revealed the polymorphic amyloidogenesis of b2m.ITC-based assay provides a powerful method for the study of the thermodynamics, kinetics, and mechanism of protein aggregation.