Institute of High Pressure Physics, Polish Academy of Sciences, Sokolowska 29/37, 01-142 Warsaw, Poland.
Institute of Biotechnology and Antibiotics, Staroscinska 5, 02-516 Warsaw, Poland.
Sci Rep. 2016 Aug 25;6:32022. doi: 10.1038/srep32022.
Typically, elongation of an amyloid fibril entails passing conformational details of the mother seed to daughter generations of fibrils with high fidelity. There are, however, several factors that can potentially prevent such transgenerational structural imprinting from perpetuating, for example heterogeneity of mother seeds or so-called conformational switching. Here, we examine phenotypic persistence of bovine insulin amyloid ([BI]) upon multiple rounds of self-seeding under quiescent conditions. According to infrared spectroscopy, with the following passages of homologous seeding, daughter fibrils gradually depart from the mother seed's spectral characteristics. We note that this transgenerational structural drift in [BI] amyloid leads toward fibrils with infrared, chiroptical, and morphological traits similar to those of the superstructural variant of fibrils which normally forms upon strong agitation of insulin solutions. However, in contrast to agitation-induced insulin amyloid, the superstructural assemblies of daughter fibrils isolated through self-seeding are sonication-resistant. Our results suggest that formation of single amyloid fibrils is not a dead-end of the amyloidogenic self-assembly. Instead, the process appears to continue toward the self-assembly of higher-order structures although on longer time-scales. From this perspective, the fast agitation-induced aggregation of insulin appears to be a shortcut to amyloid superstructures whose formation under quiescent conditions is slow.
通常情况下，淀粉样纤维的延伸需要以高度保真度将母种的构象细节传递给纤维的子代。然而，有几个因素可能会阻止这种跨代结构印迹的延续，例如母种的异质性或所谓的构象转换。在这里，我们研究了牛胰岛素淀粉样物 ([BI]) 在静止条件下多次自种情况下的表型持久性。根据红外光谱，随着同源种的后续传递，子纤维逐渐偏离母种的光谱特征。我们注意到，[BI] 淀粉样纤维的这种跨代结构漂移导致形成的纤维具有与通常在胰岛素溶液强烈搅拌下形成的纤维超结构变体相似的红外、手性和形态特征。然而，与搅拌诱导的胰岛素淀粉样物形成不同，通过自种分离的子纤维的超结构组装对超声处理具有抗性。我们的结果表明，形成单根淀粉样纤维并不是淀粉样聚集自组装的终点。相反，尽管时间尺度更长，但该过程似乎会继续朝着更高阶结构的自组装方向发展。从这个角度来看，快速搅拌诱导的胰岛素聚集似乎是淀粉样超结构的捷径，而在静止条件下形成淀粉样超结构的速度较慢。
