Institute of Physical Chemistry, Bulgarian Academy of Sciences, ul. Acad. G. Bonchev 11, Sofia 1113, Bulgaria.
J Chem Phys. 2010 Jun 7;132(21):215101. doi: 10.1063/1.3447891.
We consider nucleation of amyloid fibrils in the case when the process occurs by the mechanism of direct polymerization of practically fully extended protein segments, i.e., beta-strands, into beta-sheets. Applying the classical nucleation theory, we derive a general expression for the work to form a nanosized amyloid fibril (protofilament) constituted of successively layered beta-sheets. Analysis of this expression reveals that with increasing its size, the fibril transforms from one-dimensional to two-dimensional aggregate in order to preserve the equilibrium shape corresponding to minimal formation work. We determine the size of the fibril nucleus, the fibril nucleation work, and the fibril nucleation rate as explicit functions of the concentration and temperature of the protein solution. The results obtained are applicable to homogeneous nucleation, which occurs when the solution is sufficiently pure and/or strongly supersaturated.
我们研究了在蛋白质片段（如β-折叠）几乎完全伸展的情况下，通过直接聚合机制形成淀粉样原纤维的成核过程。应用经典成核理论，我们推导出了由相继堆积的β-折叠层组成的纳米级淀粉样原纤维（原纤维丝）形成的功的一般表达式。对该表达式的分析表明，随着其尺寸的增加，原纤维从一维转变为二维聚集体，以保持与最小形成功对应的平衡形状。我们将原纤维核的大小、原纤维成核功和原纤维成核速率确定为蛋白质溶液浓度和温度的显函数。所得结果适用于均相成核，即当溶液足够纯净和/或过饱和度较强时发生的成核。
