We demonstrate a solution method that allows both elongation rate and average fibril length of assembling amyloid fibrils to be estimated. The approach involves acquisition of real-time neutron scattering data during the initial stages of seeded growth, using contrast matched buffer to make the seeds effectively invisible to neutrons. As deuterated monomers add on to the seeds, the labelled growing ends give rise to scattering patterns that we model as cylinders whose increase in length with time gives an elongation rate. In addition, the absolute intensity of the signal can be used to determine the number of growing ends per unit volume, which in turn provides an estimate of seed length. The number of ends did not change significantly during elongation, demonstrating that any spontaneous or secondary nucleation was not significant compared with growth on the ends of pre-existing fibrils, and in addition providing a method of internal validation for the technique. Our experiments on initial growth of alpha synuclein fibrils using 1.2 mg ml⁻¹ seeds in 2.5 mg ml⁻¹ deuterated monomer at room temperature gave an elongation rate of 6.3 ± 0.5 Å min⁻¹, and an average seed length estimate of 4.2 ± 1.3 μm.

中文翻译：

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使用同位素标记的小角中子散射测定溶液中淀粉样原纤维的伸长率和平均长度

我们展示了一种解决方法，可以估计组装淀粉样原纤维的伸长率和平均原纤维长度。该方法涉及在种子生长的初始阶段采集实时中子散射数据，使用对比度匹配的缓冲区使种子对中子有效地不可见。当氘化单体添加到种子上时，标记的生长端会产生散射图案，我们将其建模为圆柱体，其长度随着时间的推移而增加，从而产生伸长率。此外，信号的绝对强度可用于确定每单位体积的生长端数量，从而提供种子长度的估计。伸长过程中末端数量没有显着变化，这表明与预先存在的原纤维末端的生长相比，任何自发或二次成核并不显着，此外还提供了一种对该技术进行内部验证的方法。我们在室温下使用 1.2 mg ml ^-1种子在 2.5 mg ml ^{-1氘代单体中进行α突触核蛋白原纤维的初始生长实验，得出伸长率为 6.3 ± 0.5 Å min -1}，平均种子长度估计为 4.2 ± 1.3微米。