Self-Assembling Peptides, Conjugates, and Mimics: A Versatile Platform for Materials and Beyond

Peptides are fundamental components of biological systems that are also readily synthesized chemically. Alongside polypeptides, proteins, and their mimics, peptides have emerged over the past few decades as versatile and indispensable molecular building blocks for creating myriad functional materials. While early studies on peptide assembly focused primarily on their pathological roles, such as the formation of amyloid fibrils implicated in neurodegenerative diseases, their potential as materials gained broader recognition in the 1990s. (1−5) Their ability to mediate a wide range of intermolecular interactions─hydrophobic, electrostatic, hydrogen bonding, and more─makes peptides uniquely suited not only for creating advanced functional materials with intricate internal structures and surface patterns but also for exploring fundamental scientific concepts, such as complex phase behavior and dynamic interfacial phenomena. With nearly all the chemical functionalities of proteins, but generally of smaller size and structural simplicity, peptides are readily conjugated with other moieties such as fatty acids, lipids, drugs, sugars, or synthetic macromolecules, to engineer new molecular architectures. (2,3,6) This thematic issue of Accounts of Chemical Research highlights cutting-edge peptide materials research, showcasing how these molecular building blocks are leveraged to drive innovations across diverse scientific and technological domains. The selected Accounts in this collection emphasize the chemical principles underlying the development of structures and materials formed through the self-assembly of peptides, polypeptides, proteins, and their mimics. For example, Xu and colleagues delve into enzyme-instructed self-assembly (EISA), where enzymatic reactions guide the formation of local peptide assemblies. (7) By leveraging chemistry at the molecular scale, EISA enables the creation of dynamic, stimuli-responsive materials with applications in cancer therapeutics. The insights provided by this work illuminate how enzymatic catalysis can be a powerful tool for controlling peptide assembly and functionality. Similarly, Deming highlights sulfur-containing amino acids as chemical switches that modulate polypeptide material properties under physiologically relevant conditions. (8) This strategy integrates chemical specificity with material functionality, enabling applications ranging from therapeutics to diagnostics. Next, Yan and co-workers examine the transition from ordered to disordered peptide assemblies, providing molecular-level insights into how chemical factors drive these transitions. (9) Their work highlights the potential of peptide chemistry in developing sustainable biomaterials. Building on the theme of chemical control, Yu et al. focus on collagen-inspired peptides, emphasizing their applications in regenerative medicine. (10) By detailing their synthesis, hybridization strategies, and structural properties, this Account demonstrates how precise chemical modifications can probe tissue remodeling and enable the creation of next-generation biomaterials. Along these lines, Kros and colleagues explore coiled-coil peptides in the development and functionalization of lipid nanoparticles. (11) Their Account elucidates molecular interactions that enhance drug encapsulation, targeting, and release, offering a blueprint for designing more efficient nanoparticle-based delivery systems. Further emphasizing fundamental chemical principles, Perry et al. examine complex coacervation involving oppositely charged polypeptides. (12) By dissecting the roles of charge patterning, hydrophobicity, and molecular structure, this Account provides insights vital for developing biomolecule stabilization systems and advanced drug delivery platforms. Miserez et al. explore bioinspired approaches by examining cephalopod-derived peptides. (13) These peptides serve as templates for creating materials with hierarchical structures and tunable properties, such as hydrogels and coacervates, showcasing the power of bioinspiration in materials chemistry. Chilkoti and colleagues shift the focus to synthetic intrinsically disordered proteins (SynIDPs), demonstrating how structural disorder can be harnessed to design biomaterials with unique properties. (14) This Account provides strategies for engineering protein-based systems for drug delivery and tissue engineering, bridging protein chemistry with innovative material design. Champion and co-workers expand the scope of self-assembling biomaterials with their development of self-assembled protein vesicles. (15) These vesicles, formed entirely in aqueous conditions using amphiphilic fusion proteins, showcase remarkable tunability in size, stability, and functionality. Their engineering relies on the strategic interplay of thermoresponsive elastin-like polypeptides, leucine zipper domains, and functional proteins, enabling vesicle applications ranging from drug delivery and biocatalysis to vaccines. Collectively, these Accounts illustrate how chemical design underpins innovation in creating peptide-based materials. From controlling molecular interactions to engineering stimuli-responsive systems, the featured Accounts emphasize the pivotal role of peptides, proteins, and their analogues as adaptable and versatile building blocks. As peptide materials continue to evolve, their intersection with materials chemistry offers promising advances in both fundamental understanding and practical applications. We hope this thematic issue inspires researchers to delve deeper into the materials aspects of peptides, explore new frontiers, and contribute to the growing prominence of peptides as a new cornerstone of materials science. This article references 15 other publications. This article has not yet been cited by other publications.