Tian Yu, Zhang Huixi Violet, Kiick Kristi L, Saven Jeffery G, Pochan Darrin J
Materials Science and Engineering Department, University of Delaware, Newark, Delaware 19716, USA.
Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Org Biomol Chem. 2017 Aug 7;15(29):6109-6118. doi: 10.1039/c7ob01197k. Epub 2017 Jun 22.
Natural biomolecular self-assembly typically occurs under a narrow range of solution conditions, and the design of sequences that can form prescribed structures under a range of such conditions would be valuable in the bottom-up assembly of predetermined nanostructures. We present a computationally designed peptide that robustly self-assembles into regular arrays under a wide range of solution pH and temperature conditions. Controling the solution conditions provides the opportunity to exploit a simple and reproducible approach for altering the pathway of peptide solution self-assembly. The computationally designed peptide forms a homotetrameric coiled-coil bundle that further self-assembles into 2-D plate structures with well-defined inter-bundle symmetry. Herein, we present how modulation of solution conditions, such as pH and temperature, can be used to control the kinetics of the inter-bundle assembly and manipulate the final morphology. Changes in solution pH primarily influence the inter-bundle assembly by affecting the charged state of ionizable residues on the bundle exterior while leaving the homotetrameric coiled-coil structure intact. At low pH, repulsive interactions prevent 2-D lattice nanostructure formation. Near the estimated isoelectric point of the peptide, bundle aggregation is rapid and yields disordered products, which subsequently transform into ordered nanostructures over days to weeks. At elevated temperatures (T = 40 °C or 50 °C), the formation of disordered, kinetically-trapped products largely can be eliminated, allowing the system to quickly assemble into plate-like nanostructured lattices. Moreover, subtle changes in pH and in the peptide charge state have a significant influence on the thickness of formed plates and on the hierarchical manner in which plates fuse into larger material structures with observable grain boundaries. These findings confirm the ability to finely tune the peptide assembly process to achieve a range of engineered structures with one simple 29-residue peptide building block.
天然生物分子自组装通常在狭窄的溶液条件范围内发生，而设计出能在一系列此类条件下形成特定结构的序列，对于自下而上组装预定的纳米结构将具有重要价值。我们展示了一种通过计算设计的肽，它能在广泛的溶液pH值和温度条件下稳健地自组装成规则阵列。控制溶液条件提供了一个机会，可利用一种简单且可重复的方法来改变肽溶液自组装的途径。这种通过计算设计的肽形成了一个同四聚体卷曲螺旋束，该束进一步自组装成具有明确束间对称性的二维平板结构。在此，我们展示了如何利用溶液条件（如pH值和温度）的调节来控制束间组装的动力学，并操纵最终的形态。溶液pH值的变化主要通过影响束外部可电离残基的带电状态来影响束间组装，同时保持同四聚体卷曲螺旋结构完整。在低pH值下，排斥相互作用阻止二维晶格纳米结构的形成。在接近该肽估计的等电点时，束聚集迅速并产生无序产物，这些产物随后在数天到数周内转化为有序的纳米结构。在升高的温度下（T = 40°C或50°C），无序的、动力学捕获的产物的形成在很大程度上可以消除，使系统能够快速组装成板状纳米结构晶格。此外，pH值和肽带电状态的细微变化对形成的板的厚度以及板融合成具有可观察到晶界的更大材料结构的分级方式有显著影响。这些发现证实了能够通过一个简单的29个残基的肽构建块精细调节肽组装过程，以实现一系列工程结构。
