Peptide amphiphiles (PAs) are small molecules that contain hydrophobic components covalently conjugated to peptides. In this Account, we describe recent advances involving PAs that consist of a short peptide sequence linked to an aliphatic tail. The peptide sequence can be designed to form β-sheets among the amino acids near the alkyl tail, while the residues farthest from the tail are charged to promote solubility and in some cases contain a bioactive sequence. In water, β-sheet formation and hydrophobic collapse of the aliphatic tails induce assembly of the molecules into supramolecular one-dimensional nanostructures, commonly high-aspect-ratio cylindrical or ribbonlike nanofibers. These nanostructures hold significant promise for biomedical functions due to their ability to display a high density of biological signals on their surface for targeting or to activate pathways, as well as for biocompatibility and biodegradable nature. Recent studies have shown that supramolecular systems, such as PAs, often become kinetically trapped in local minima along their self-assembly reaction coordinate, not unlike the pathways associated with protein folding. Furthermore, the assembly pathway can influence the shape, internal structure, and dimension of nanostructures and thereby affect their bioactivity. We discuss methods to map the energy landscape of a PA structure as a function of thermal energy and ionic strength and vary these parameters to convert between kinetically trapped and thermodynamically favorable states. We also demonstrate that the pathway-dependent morphology of the PA assembly can determine biological cell adhesion and survival rates. The dynamics associated with the nanostructures are also critical to their function, and techniques are now available to probe the internal dynamics of these nanostructures. For example, by conjugating radical electron spin labels to PAs, electron paramagnetic resonance spectroscopy can be used to study the rotational diffusion rates within the fiber, showing a liquidlike to solidlike transition through the cross section of the nanofiber. PAs can also be labeled with fluorescent dyes, allowing the use of super-resolution microscopy techniques to study the molecular exchange dynamics between PA fibers. For a weak hydrogen-bonding PA, individual PA molecules or clusters exchange between fibers in time scales as short as minutes. The amount of hydrogen bonding within PAs that dictates the dynamics also plays an important role in biological function. In one case, weak hydrogen bonding within a PA resulted in cell death through disruption of lipid membranes, while in another example reduced hydrogen bonding enhanced growth factor signaling by increasing lipid raft mobility. PAs are a promising platform for designing advanced hybrid materials. We discuss a covalent polymer with a rigid aromatic imine backbone and alkylated peptide side chains that simultaneously polymerizes and interacts with a supramolecular PA structure with identical chemistry to that of the side chains. The covalent polymerization can be "catalyzed" by noncovalent polymerization of supramolecular monomers, taking advantage of the dynamic nature of supramolecular assemblies. These novel hybrid structures have potential in self-repairing materials and as reusable scaffolds for delivery of drugs or other chemicals. Finally, we highlight recent biomedical applications of PAs and related structures, ranging from bone regeneration to decreasing blood loss during internal bleeding.

Mark P. Hendricks

Kohei Sato

Liam C. Palmer

Samuel I. Stupp

Accounts of Chemical Research

ACCOUNTS OF CHEMICAL RESEARCH 提供简短、简洁和批判性的文章，提供化学和生物化学所有领域的基础研究和应用的易于阅读的概述。此外，ACCOUNTS OF CHEMICAL RESEARCH 还出版了专门针对具有不寻常活动和意义的单一问题的特刊。访问 ACCOUNTS SPECIAL ISSUES 页面，查看所有特殊问题的列表、描述和 TOC。从 2008 年开始，ACCOUNTS OF CHEMICAL RESEARCH 将其传统的文章摘要替换为文章“CONSPECTUS”。这些新条目概述了研究，使读者可以更仔细地了解文章的内容和意义。通过对文章内容的更详细描述，CONSPECTUS 提高了文章在搜索引擎中的可发现性和研究的曝光率。

Accounts of Chemical Research publishes concise, clear, and critical articles that provide accessible overviews of fundamental research and applications across all areas of chemistry and biochemistry. Additionally, Accounts of Chemical Research publishes special issues focused on single topics of unusual activity and significance. You can visit the Accounts of Chemical Research Special Issues page to view a list of all special issues, their descriptions, and tables of contents. Since 2008, Accounts of Chemical Research has replaced traditional article abstracts with 'CONSPECTUS.' These new entries summarize the research, allowing readers to gain a deeper understanding of the content and significance of the articles. By providing a more detailed description of the article content, CONSPECTUS enhances the discoverability of articles in search engines and increases the visibility of the research.

《Accounts of Chemical Research》提供简短、清晰且具有批判性的文章，涵盖化学和生物化学各个领域的基础研究和应用，旨在为读者提供易于理解的概述。此外，《Accounts of Chemical Research》还出版专门针对具有特殊活动和重要性的单一主题的特刊。您可以访问《Accounts of Chemical Research》特刊页面，查看所有特刊的列表、描述和目录。从2008年开始，《Accounts of Chemical Research》将传统的文章摘要替换为“CONSPECTUS”，这些新条目概述了研究内容，使读者能够更深入地理解文章的内容和意义。通过对文章内容的详细描述，CONSPECTUS提高了文章在搜索引擎中的可发现性和研究的曝光率。

Acc. Chem. Res.

Supramolecular Assembly of Peptide Amphiphiles

It is demonstrated that the pathway-dependent morphology of the PA assembly can determine biological cell adhesion and survival rates, and methods to map the energy landscape of a PA structure as a function of thermal energy and ionic strength are discussed, to convert between kinetically trapped and thermodynamically favorable states.

Category	Quartile
化学	1
化学, 化学综合	1

Supramolecular Assembly of Peptide Amphiphiles

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Journal Info

Category	Quartile
CHEMISTRY, MULTIDISCIPLINARY	1