Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Nat Chem. 2016 Nov;8(11):1008-1014. doi: 10.1038/nchem.2556. Epub 2016 Jul 11.
Sticky-ended DNA duplexes can associate spontaneously into long double helices; however, such self-assembly is much less developed with proteins. Collagen is the most prevalent component of the extracellular matrix and a common clinical biomaterial. As for natural DNA, the 10-residue triple helices (300 nm) of natural collagen are recalcitrant to chemical synthesis. Here we show how the self-assembly of short collagen-mimetic peptides (CMPs) can enable the fabrication of synthetic collagen triple helices that are nearly a micrometre in length. Inspired by the mathematics of tessellations, we derive rules for the design of single CMPs that self-assemble into long triple helices with perfect symmetry. Sticky ends thus created are uniform across the assembly and drive its growth. Enacting this design yields individual triple helices that, in length, match or exceed those in natural collagen and are remarkably thermostable, despite the absence of higher-order association. The symmetric assembly of CMPs provides an enabling platform for the development of advanced materials for medicine and nanotechnology.
粘性末端的 DNA 双链可以自发地缔合成长的双螺旋；然而，蛋白质的这种自组装能力要差得多。胶原蛋白是细胞外基质中最普遍的成分，也是一种常见的临床生物材料。与天然 DNA 一样，天然胶原蛋白的10 残基三螺旋（300nm）对化学合成具有很强的抵抗力。在这里，我们展示了短胶原模拟肽（CMP）的自组装如何能够制造出长度接近一微米的合成胶原三螺旋。受嵌合体数学的启发，我们推导出了设计能够自组装成长度具有完美对称性的长三螺旋的单个 CMP 的规则。因此，形成的粘性末端在整个组装过程中是均匀的，并驱动其生长。执行这种设计会产生单个三螺旋，其长度与天然胶原蛋白中的三螺旋相匹配或超过天然胶原蛋白中的三螺旋，并且尽管没有更高阶的缔合，但其热稳定性却非常显著。CMP 的对称组装为开发用于医学和纳米技术的先进材料提供了一个可行的平台。
