Molecular Insights into the Self-Assembly of Block Copolymer Suckerin Polypeptides into Nanoconfined β-Sheets.

Abstract

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.