Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, United States.
Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States.
J Am Chem Soc. 2022 Sep 14;144(36):16512-16523. doi: 10.1021/jacs.2c05759. Epub 2022 Sep 1.
Pathways in supramolecular polymerization traverse different regions of the system's energy landscape, affecting not only their architectures and internal structure but also their functions. We report here on the effects of pathway selection on polymerization for two isomeric peptide amphiphile monomers with amino acid sequences AAEE and AEAE. We subjected the monomers to five different pathways that varied in the order they were exposed to electrostatic screening by electrolytes and thermal annealing. We found that introducing electrostatic screening of E residues before annealing led to crystalline packing of AAEE monomers. Electrostatic screening decreased intermolecular repulsion among AAEE monomers thus promoting internal order within the supramolecular polymers, while subsequent annealing brought them closer to thermodynamic equilibrium with enhanced β-sheet secondary structure. In contrast, supramolecular polymerization of AEAE monomers was less pathway dependent, which we attribute to side-chain dimerization. Regardless of the pathway, the internal structure of AEAE nanostructures had limited internal order and moderate β-sheet structure. These supramolecular polymers generated hydrogels with lower porosity and greater bulk mechanical strength than those formed by the more cohesive AAEE polymers. The combination of dynamic, less ordered internal structure and bulk strength of AEAE networks promoted strong cell-material interactions in adherent epithelial-like cells, evidenced by increased cytoskeletal remodeling and cell spreading. The highly ordered AAEE nanostructures formed porous hydrogels with inferior bulk mechanical properties and weaker cell-material interactions. We conclude that pathway sensitivity in supramolecular synthesis, and therefore structure and function, is highly dependent on the nature of dominant interactions driving polymerization.
超分子聚合途径贯穿了体系能量景观的不同区域，不仅影响了它们的结构和内部结构，还影响了它们的功能。我们在此报告了两种具有 AAEE 和 AEAE 氨基酸序列的异构肽两亲单体的聚合途径选择对聚合的影响。我们对单体进行了五种不同途径的处理，这些途径在暴露于电解质静电屏蔽和热退火的顺序上有所不同。我们发现，在退火之前引入 E 残基的静电屏蔽会导致 AAEE 单体的结晶堆积。静电屏蔽降低了 AAEE 单体之间的分子间斥力，从而促进了超分子聚合物内部的有序性，而随后的退火使它们更接近热力学平衡，增强了β-折叠二级结构。相比之下，AEAE 单体的超分子聚合对途径的依赖性较小，这归因于侧链二聚化。无论途径如何，AEAE 纳米结构的内部结构都具有有限的内部有序性和适度的β-折叠结构。与更具内聚性的 AAEE 聚合物形成的水凝胶相比，这些超分子聚合物生成的水凝胶具有较低的孔隙率和更大的体力学强度。AEAE 网络的动态、无序的内部结构和体力学强度的结合促进了贴壁上皮样细胞中的强细胞-材料相互作用，这表现为细胞骨架重塑和细胞铺展的增加。高度有序的 AAEE 纳米结构形成了具有较差体力学性能和较弱细胞-材料相互作用的多孔水凝胶。我们得出结论，超分子合成中的途径敏感性以及因此结构和功能高度依赖于驱动聚合的主导相互作用的性质。
