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Title: Supramolecular Assembly of Peptide Amphiphiles

Abstract

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 ofmore » 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.« less

Authors:
ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [3]
  1. Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States
  2. Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States, Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States
  3. Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, Illinois 60611, United States, Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States, Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois 60208, United States, Department of Medicine, Northwestern University, Chicago, Illinois 60611, United States, Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, United States
Publication Date:
Research Org.:
Northwestern Univ., Evanston, IL (United States); Energy Frontier Research Centers (EFRC) (United States). Center for Bio-Inspired Energy Science (CBES)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health (NIH) (United States); National Science Foundation (NSF)
OSTI Identifier:
1380069
Alternate Identifier(s):
OSTI ID: 1507569
Grant/Contract Number:  
SC0000989; FG02-00ER45810; 5R01DE015920-9; 5R01EB003806-09; 5R01HL116577-02; F5U54CA151880-05; P01HL108795-04; DMR-1508731
Resource Type:
Journal Article: Published Article
Journal Name:
Accounts of Chemical Research
Additional Journal Information:
Journal Name: Accounts of Chemical Research Journal Volume: 50 Journal Issue: 10; Journal ID: ISSN 0001-4842
Publisher:
American Chemical Society
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Hendricks, Mark P., Sato, Kohei, Palmer, Liam C., and Stupp, Samuel I. Supramolecular Assembly of Peptide Amphiphiles. United States: N. p., 2017. Web. doi:10.1021/acs.accounts.7b00297.
Hendricks, Mark P., Sato, Kohei, Palmer, Liam C., & Stupp, Samuel I. Supramolecular Assembly of Peptide Amphiphiles. United States. https://doi.org/10.1021/acs.accounts.7b00297
Hendricks, Mark P., Sato, Kohei, Palmer, Liam C., and Stupp, Samuel I. Wed . "Supramolecular Assembly of Peptide Amphiphiles". United States. https://doi.org/10.1021/acs.accounts.7b00297.
@article{osti_1380069,
title = {Supramolecular Assembly of Peptide Amphiphiles},
author = {Hendricks, Mark P. and Sato, Kohei and Palmer, Liam C. and Stupp, Samuel I.},
abstractNote = {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.},
doi = {10.1021/acs.accounts.7b00297},
url = {https://www.osti.gov/biblio/1380069}, journal = {Accounts of Chemical Research},
issn = {0001-4842},
number = 10,
volume = 50,
place = {United States},
year = {2017},
month = {9}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at https://doi.org/10.1021/acs.accounts.7b00297

Citation Metrics:
Cited by: 39 works
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Figures / Tables:

Figure 1. Figure 1.: General structure of a PA (center) surrounded by many of the supramolecular nanostructures that have been formed from this system.

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Works referencing / citing this record:

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Halogen bonding at the wet interfaces of an amyloid peptide structure
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In Situ Self‐Assembled Nanofibers Precisely Target Cancer‐Associated Fibroblasts for Improved Tumor Imaging
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Hierarchical Self-Assembly of BODIPY Dyes as a Tool to Improve the Antitumor Activity of Capsaicin in Prostate Cancer
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In Situ Self‐Assembled Nanofibers Precisely Target Cancer‐Associated Fibroblasts for Improved Tumor Imaging
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Self‐assembly of a Sequence‐shuffled Short Peptide Amphiphile Triggered by Metal Ions into Terraced Nanodome‐like Structures
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Functional Control of Peptide Amphiphile Assemblies via Modulation of Internal Cohesion and Surface Chemistry Switch
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Luminescent Ultralong Microfibers Prepared through Supramolecular Self-Assembly of Lanthanide Ions and Thymidine in Water
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Glycine Substitution Effects on the Supramolecular Morphology and Rigidity of Cell‐Adhesive Amphiphilic Peptides
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C 3 ‐Symmetrical π‐Scaffolds: Useful Building Blocks to Construct Helical Supramolecular Polymers
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Two-Step Assembly of Thermoresponsive Gold Nanorods Coated with a Single Kind of Ligand
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Peptide Nanomaterials Designed from Natural Supramolecular Systems
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Nanomaterials for Wound Healing
book, December 2019


One-pot universal initiation-growth methods from a liquid crystalline block copolymer
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Anisotropic polymer nanoparticles with controlled dimensions from the morphological transformation of isotropic seeds
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Supramolecular scaffolds enabling the controlled assembly of functional molecular units
journal, January 2018


Immunomodulatory vasoactive intestinal peptide amphiphile micelles
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Directing an oligopeptide amphiphile into an aligned nanofiber matrix for elucidating molecular structures
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Molecular simulations of self-assembling bio-inspired supramolecular systems and their connection to experiments
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Multicomponent peptide assemblies
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Multicomponent self-assembly as a tool to harness new properties from peptides and proteins in material design
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A self-assembling peptide hydrogel for ultrarapid 3D bioassays
journal, January 2019


Self-assembly of model short triblock amphiphiles in dilute solution
journal, January 2018


In situ fabrication of multifunctional gold–amino acid superstructures based on self-assembly
journal, January 2019


Peptide nucleic acids harness dual information codes in a single molecule
journal, January 2020


Supramolecular materials based on AIE luminogens (AIEgens): construction and applications
journal, January 2020


Supramolecular assembly of functional peptide–polymer conjugates
journal, January 2019


Hydrogen-bonding regulated assembly of molecular and macromolecular amphiphiles
journal, January 2019


Secondary structure of end group functionalized oligomeric- l -lysines: investigations of solvent and structure dependent helicity
journal, January 2019


Sequence isomerism-dependent self-assembly of glycopeptide mimetics with switchable antibiofilm properties
journal, January 2019


Designing stable, hierarchical peptide fibers from block co-polypeptide sequences
journal, January 2019


Directional molecular sliding movement in peptide hydrogels accelerates cell proliferation
journal, January 2020


The pathway and kinetics of hierarchical assembly of ionic oligomers into a lyotropic columnar phase
journal, January 2019


A self-assembling amphiphilic peptide nanoparticle for the efficient entrapment of DNA cargoes up to 100 nucleotides in length
journal, January 2020


Interaction of phospholipid vesicles with gemini surfactants of different lysine spacer lengths
journal, January 2019


A self-assembled peptide hydrogel for cytokine sequestration
journal, January 2020


Self-Assembly and Applications of Amphiphilic Hybrid POSS Copolymers
journal, September 2018


    Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.