Suckerin in squid sucker ring teeth is a block-copolymer peptide comprised of two repeating modules—the alanine and histidine-rich M1 and the glycine-rich M2. Suckerin self-assemblies display excellent thermo-plasticity and pH-responsive properties, along with the high biocompatibility, biodegradability, and sustainability. However, the self-assembly mechanism and the detailed role of each module are still elusive, limiting the capability of applying and manipulating such biomaterials. Here, the self-assembly dynamics of the two modules and two minimalist suckerin-mimetic block-copolymers, M1-M2-M1 and M2-M1-M2, in silico is investigated. The simulation results demonstrate that M2 has a stronger self-association but weaker β-sheet propensities than M1. The high self-assembly propensity of M2 allows the minimalist block-copolymer peptides to coalesce with microphase separation, enabling the formation of nanoconfined β-sheets in the matrix formed by M1–M2 contacts. Since these glycine-rich fragments with scatted hydrophobic and aromatic residues are building blocks of many other block-copolymer peptides, the study suggests that these modules function as the “molecular glue” in addition to the flexible linker or spacer to drive the self-assembly and microphase separation. The uncovered molecular insights may help understand the structure and function of suckerin and also aid in the design of functional block-copolymer peptides for nanotechnology and biomedicine applications.

中文翻译：

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嵌段共聚物 Suckerin 多肽自组装成纳米限制 β-片层的分子洞察

鱿鱼吸盘环齿中的吸盘蛋白是一种嵌段共聚物肽，由两个重复模块组成：富含丙氨酸和组氨酸的 M1 以及富含甘氨酸的 M2。Suckerin 自组装体表现出优异的热塑性和 pH 响应特性，以及高生物相容性、生物降解性和可持续性。然而，自组装机制和每个模块的详细作用仍然难以捉摸，限制了应用和操纵此类生物材料的能力。在这里，研究了两个模块和两种极简模拟吸盘嵌段共聚物 M1-M2-M1 和 M2-M1-M2 的计算机自组装动力学。模拟结果表明，M2 比 M1 具有更强的自缔合性，但 β 折叠倾向更弱。M2 的高自组装倾向使得极简嵌段共聚物肽能够通过微相分离聚结，从而能够在 M1-M2 接触形成的基质中形成纳米限制的 β-折叠。由于这些富含甘氨酸的片段具有分散的疏水性和芳香族残基，是许多其他嵌段共聚物肽的构建模块，因此研究表明，除了柔性接头或间隔基之外，这些模块还充当“分子胶”来驱动自组装和微相分离。未发现的分子见解可能有助于理解吸盘蛋白的结构和功能，也有助于设计用于纳米技术和生物医学应用的功能性嵌段共聚物肽。