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. 2024 Aug 7;146(31):21555-21567. doi: 10.1021/jacs.4c05170. Epub 2024 Jul 25.
Transforming growth factor (TGF)-β1 is a multifunctional protein that is essential in many cellular processes that include fibrosis, inflammation, chondrogenesis, and cartilage repair. In particular, cartilage repair is important to avoid physical disability since this tissue does not have the inherent capacity to regenerate beyond full development. We report here on supramolecular coassemblies of two peptide amphiphile molecules, one containing a TGF-β1 mimetic peptide, and another which is one of two constitutional isomers lacking bioactivity. Using human articular chondrocytes, we investigated the bioactivity of the supramolecular copolymers of each isomer displaying either the previously reported linear form of the mimetic peptide or a novel cyclic analogue. Based on fluorescence depolarization and H NMR spin-lattice relaxation times, we found that coassemblies containing the cyclic compound and the most dynamic isomer exhibited the highest intracellular TGF-β1 signaling and gene expression of cartilage extracellular matrix components. We conclude that control of supramolecular motion is emerging as an important factor in the binding of synthetic molecules to receptors that can be tuned through chemical structure.
转化生长因子 (TGF)-β1 是一种多功能蛋白，在许多细胞过程中都很重要，包括纤维化、炎症、软骨生成和软骨修复。特别是，软骨修复对于避免身体残疾很重要，因为这种组织在完全发育后没有内在的再生能力。我们在这里报告了两种肽两亲分子的超分子共组装，一种含有 TGF-β1 模拟肽，另一种是两种无生物活性的结构异构体之一。使用人关节软骨细胞，我们研究了每个异构体的超分子共聚物的生物活性，这些共聚物分别显示出先前报道的模拟肽的线性形式或新颖的环状类似物。基于荧光各向异性和 H NMR 自旋晶格弛豫时间，我们发现含有环状化合物和最动态异构体的共组装表现出最高的细胞内 TGF-β1 信号和软骨细胞外基质成分的基因表达。我们得出结论，控制超分子运动正在成为合成分子与受体结合的一个重要因素，这种结合可以通过化学结构进行调节。
