The ability to self-propagate is one of the most intriguing characteristics of amyloid fibrils, and is a feature of great interest both to stopping unwanted pathological amyloid, and for engineering functional amyloid as a useful nanomaterial. The sequence and structural tolerances for amyloid seeding are not well understood, particularly concerning the propagation of distinct fibril morphologies (polymorphs) across species. This study examined the seeding and cross-seeding reactions between two unique fibril polymorphs, one long and flexible (formed at pH 2) and the other short and rigid (formed at pH 6.3), of human lysozyme and hen egg-white lysozyme. Both polymorphs could cross-seed aggregation across species, but this reaction was markedly reduced under physiological conditions. For both species, the pH 6.3 fibril polymorph was dominant, seeding fibril growth with a faster growth rate constant at pH 2 than the pH 2 polymorph. Based on fibrillation kinetics and fibril morphology, we found that the pH 2 polymorph was not able to faithfully replicate itself at pH 6.3. These results show that two distinct amyloid polymorphs are both capable of heterologous seeding across two species (human and hen) of lysozyme, but that the pH 6.3 polymorph is favored, regardless of the species, likely due to a lower energy barrier, or faster configurational diffusion, to accessing this particular misfolded form. These findings contribute to our better understanding of amyloid strain propagation across species barriers.

自我传播的能力是淀粉样蛋白原纤维最引人入胜的特征之一，并且对阻止有害的病理性淀粉样蛋白以及将功能性淀粉样蛋白工程化为有用的纳米材料都引起了极大的兴趣。淀粉样蛋白播种的顺序和结构耐受性尚未得到很好的理解，特别是关于物种间不同的原纤维形态（多态）的传播。这项研究检查了人类溶菌酶和鸡蛋清溶菌酶的两种独特的原纤维多晶型物的播种和交叉播种反应，一种长而有弹性（在pH 2下形成），另一种又短又硬（在pH 6.3下形成）。两种多晶型物都可以跨种子跨种聚集，但是在生理条件下该反应明显减少。对于这两种物种，pH 6.3的原纤维多晶型均占优势，种子原纤维的生长在pH 2处比在pH 2多晶型物中具有更快的生长速率常数。基于原纤化动力学和原纤维形态，我们发现pH 2多晶型物不能在pH 6.3时忠实地自我复制。这些结果表明，两种截然不同的淀粉样蛋白多态性都能够跨两种溶菌酶物种（人和母鸡）异种播种，但无论哪种物种，pH 6.3多晶型物都是有利的，这可能是由于较低的能垒或更快的构型扩散，以获取这种特殊的错误折叠形式。这些发现有助于我们更好地了解淀粉样菌株跨物种屏障的传播。我们发现pH 2的多晶型物无法在pH 6.3的情况下忠实地复制自身。这些结果表明，两种不同的淀粉样蛋白多态性都能够跨溶菌酶的两个物种（人和母鸡）异种接种，但是无论哪种物种，pH 6.3的多态性都是有利的，这可能是由于较低的能垒或更快的构型扩散，以获取这种特殊的错误折叠形式。这些发现有助于我们更好地了解淀粉样菌株跨物种屏障的传播。我们发现pH 2的多晶型物无法在pH 6.3的情况下忠实地复制自身。这些结果表明，两种不同的淀粉样蛋白多态性都能够跨溶菌酶的两个物种（人和母鸡）异种接种，但是无论哪种物种，pH 6.3的多态性都是有利的，这可能是由于较低的能垒或更快的构型扩散，以获取这种特殊的错误折叠形式。这些发现有助于我们更好地了解淀粉样菌株跨物种屏障的传播。访问这种特殊的错误折叠形式。这些发现有助于我们更好地了解淀粉样菌株跨物种屏障的传播。访问这种特殊的错误折叠形式。这些发现有助于我们更好地了解淀粉样菌株跨物种屏障的传播。