Department of Chemistry, Haverford College, Haverford, Pennsylvania 19041, United States.
Department of Biochemistry and Structural Biology, Centre for Molecular Protein Science, Lund University, Lund SE-22100, Sweden.
Biomacromolecules. 2020 Dec 14;21(12):4781-4794. doi: 10.1021/acs.biomac.0c00989. Epub 2020 Nov 10.
Self-assembling peptide-based hydrogels are a class of tunable soft materials that have been shown to be highly useful for a number of biomedical applications. The dynamic formation of the supramolecular fibrils that compose these materials has heretofore remained poorly characterized. A better understanding of this process would provide important insights into the behavior of these systems and could aid in the rational design of new peptide hydrogels. Here, we report the determination of the microscopic steps that underpin the self-assembly of a hydrogel-forming peptide, SgI. Using theoretical models of linear polymerization to analyze the kinetic self-assembly data, we show that SgI fibril formation is driven by fibril-catalyzed secondary nucleation and that all the microscopic processes involved in SgI self-assembly display an enzyme-like saturation behavior. Moreover, this analysis allows us to quantify the rates of the underlying processes at different peptide concentrations and to calculate the time evolution of these reaction rates over the time course of self-assembly. We demonstrate here a new mechanistic approach for the study of self-assembling hydrogel-forming peptides, which is complementary to commonly used materials science characterization techniques.
基于自组装肽的水凝胶是一类可调软物质，已被证明在许多生物医学应用中非常有用。组成这些材料的超分子原纤维的动态形成迄今为止仍未得到很好的描述。更好地了解这一过程将为这些系统的行为提供重要的见解，并有助于新的肽水凝胶的合理设计。在这里，我们报告了支撑水凝胶形成肽 SgI 自组装的微观步骤的确定。使用线性聚合的理论模型来分析动力学自组装数据，我们表明 SgI 原纤维的形成是由原纤维催化的二次成核驱动的，并且 SgI 自组装涉及的所有微观过程都表现出类似酶的饱和行为。此外，这种分析使我们能够在不同的肽浓度下量化潜在过程的速率，并计算自组装过程中这些反应速率的时间演变。我们在这里展示了一种研究自组装水凝胶形成肽的新的机制方法，该方法与常用的材料科学表征技术互补。
