Self-assembling peptides are an exemplary class of supramolecular biomaterials of broad biomedical utility. Mechanistic studies on the peptide self-assembly demonstrated the importance of the oligomeric intermediates towards the properties of the supramolecular biomaterials being formed. In this study, we demonstrate how the overall yield of the supramolecular assemblies are moderated through subtle molecular changes in the peptide monomers. This strategy is exemplified with a set of surfactant-like peptides (SLPs) with different β-sheet propensities and charged residues flanking the aggregation domains. By integrating different techniques, we show that these molecular changes can alter both the nucleation propensity of the oligomeric intermediates and the thermodynamic stability of the fibril structures. We demonstrate that the amount of assembled nanofibers are critically defined by the oligomeric nucleation propensities. Our findings offer guidance on designing self-assembling peptides for different biomedical applications, as well as insights into the role of protein gatekeeper sequences in preventing amyloidosis.

自组装肽是一类具有广泛生物医学用途的超分子生物材料的示例。对肽自组装的机理研究证明了低聚中间体对正在形成的超分子生物材料的性质的重要性。在这项研究中，我们展示了如何通过肽单体的细微分子变化来调节超分子组装体的总产量。该策略以一组具有不同 β-折叠倾向和聚合域侧翼带电残基的表面活性剂样肽 (SLP) 为例。通过整合不同的技术，我们表明这些分子变化可以改变低聚中间体的成核倾向和原纤维结构的热力学稳定性。我们证明组装纳米纤维的数量是由低聚成核倾向严格定义的。我们的研究结果为设计用于不同生物医学应用的自组装肽提供了指导，并深入了解了蛋白质看门人序列在预防淀粉样变性中的作用。