Molecular-Level Design Principles and Strategies of Peptide Self-Assembly Nanomaterials: From Sequence Engineering to Functional Applications

Peptide self-assembly has emerged as a pivotal strategy for constructing biomimetic functional materials, demonstrating extensive application potential in biomedicine and materials science owing to its superior biocompatibility, structural programmability, and dynamic tunability. Despite significant advances in this field, a comprehensive synthesis of molecular mechanisms and design methodologies remains lacking. This paper presents, for the first time, a systematic overview grounded in the hierarchical design of polypeptide molecules, elucidating key principles and strategies for engineering self-assembled peptide materials. This paper, for the first time, starts from the hierarchical design of polypeptide molecules and systematically sorts out the design principles and strategies of self-assembled peptide materials: from intramolecular factors such as amino acid sequence regulation, amphiphilic balance and chirality induction, to the hierarchical assembly mechanism driven by non-covalent interactions such as hydrogen bonds, hydrophobic interactions and π - π stacking. The influence of molecular engineering methods such as cofactor modification and co-assembly modification on the fine regulation of structure and function was further explored. Particular emphasis was placed on the methodological innovation of de novo design and bioinformatics aided design in the construction of self-assembled peptides, providing new ideas for achieving structural prediction and function-oriented design. This paper aims to construct a systematic strategy system from molecular basis to design framework, filling the gap in the summary of design methods in this field, and providing theoretical basis and design guidelines for the precise construction and functional expansion of polypeptide self-assembled materials.