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Peptoid Nanosheets | |
Peptoid nanosheets are a supramolecular assembly of a sequence-defined peptoid polymer. These peptoids have a repeating sequence pattern of ionic and hydrophobic monomers. This creates an amphiphilic polymer chain, which can stretch out and align with neighboring chains to create an extended planar assembly. Peptoid nanosheets are exciting because they can be easily synthesized and are tolerant to structural modification. They are a promising platform for building more complex nanostructures. We hope to engineer them to create materials that can mimic the molecular recogntion and catalytic properties of proteins, yet are much more stable.
Molecular structure of nanosheet-forming peptoids:
"Block-28" peptoid is our prototypic nanosheet-forming peptoid. It is a 28mer, comprised of only 3 monomers: aromatic (Npe), anionic (Nce) and cationic (Nae). They are arranged in a two-fold perdiodic sequence pattern, alternating between a polar and a non-polar monomer. The charged groups are segregated into separate blocks, resulting in an amphiphilic structure with oppositely charged halves along the backbone. The alternating monomer pattern results in polar and non-polar groups on opposite sides of the molecule along its width. Both of these are critical to its ability to assemble into nanosheets. The Sigma strand backbone conformation enables adjacent sidechains to point in opposite directions. |
Yellow = carbon, blue = nitrogen, red = oxygen. |
Block-28 chemical structure: (Nae-Npe)7-(Nce-Npe)7
Block-28 spacefilling representation:
Nanosheet under the microscope:
| Fluorescence microscopy | Atomic force microscopy (AFM) | Scanning electron microscopy (SEM) |
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| Nanosheets can be stained with hydrophobic dyes like Nile Red,and can be readily imaged on a fluorecence microscope. The sheets are placed on a think slice of agarose gel, which serves to support the sheets in a single plane. | Nanosheets can be deposited on a mica and vlsualized by AFM. This provides a good measure of the nanosheet thickness, which is about 2.7 nm. | SEM reveals sharp edges and folds within the material. |
Aberration-corrected |
Free-floating nanosheets (32 sec) |
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| Abberation-corrected TEM of a nanosheet supported on a holey carbon grid indicates alignment of chains running parallel to one another, separated by a distance of 4.5 Angstrom. | Nanosheets are free-floating in water and can be made in high yield. Here we pan over a large sample of nanosheets so you can get a sense of the uniformity/heterogeneity. |
Computational modeling of nanosheets:
Bilayer Architecture: Molecular dynamics simulations provide an atomic-level view of the molecular structure. The peptoids in the nanosheet align parallel to one another in a brick-like pattern. Two layers face each other, such that the hydrophobic aromatic groups are buried in the center and the polar groups face outward toward solvent. Download the molecular srtucture of a section of a nanosheet with water molecules here (in a .pdb file format, viewable in PyMol): nanosheet.pdb (structure v6 from the Nature paper below)
| Molecular dynamics simulation (42 sec) | Tour of the atomic structure (57 sec) |  3D backbone model |
A simulation of a peptoid nanosheet, shown first from a top-down view with the peptoid backbones colored to highlight their snake-like structure. The view then rotates to the side, and finally transitions to an all-atom representation. |
Take a closer look at the nanoscale architecture of the nanosheet and examine how backbones and sidechains are organized. | The framework of the nanosheet is based on a bilayer of parallel chains arranged in a brick-like pattern. Here is a small sub-section of a nanosheet, showing only the backbone arrgement of the chains. Use your mouse to rotate the molecular structures in 3D! Scroll to zoom. |
| MD simulation: side-view close-up (16 sec) | MD simulation: a single strand top view (7 sec) | MD simulation: Sigma sheet top view (9 sec) |
| This side-view shows how liquid-like the aromatic core is (yellow), and by contrast, how relatively stiff the backbone is (green). Here is a similar side view of the nanosheet jiggling, but just showing one isolated chain. | An individual chain is tightly embedded and as a result the backbone doesn't move us much as the smaller sidechains. | The sigma sheet motif has alternating rotational states (alpha-D and C7-beta) that are colored blue and red. By alternating back and forth between these two states, , the backbone can achieve an overall straight extent, even though locally it is a serpentine path. |
Sigma strand: The individual peptoid chains within a nanosheet adopt a snake-like shape called a sigma strand.
| Major backbone conformations | Model of the Sigma strand |
Dipeptoid Ramachandran plot (trans) |
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| The peptoid backbone shown in the two lowest energy conformations, alpha-D and C7-beta, which are near mirror images of one another. | An accurate molecular model of a sarcosine (N-methylglycine) pentamer in the sigma strand conformation. Use your mouse to rotate the molecular structures in 3D! Scroll to zoom |
The Ramachandran plot of the trans conformation of a peptoid (sarcosine) dimer. There two most stable conformers, alpha-D and C7-beta, are labeled. These alternate, swithching back and forth from one monomer to the next. |
Single-chain collapse: Prior to assembly into nanosheets, the Block-28 peptoid likely exists in a micellar state. Coarse-grained computer simulations predict that the chain collapses into a single-chain globule.
Simulation of a single chain collapse |
Single-chain globule model in water |
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A single nanosheet-forming peptoid chain, when free in aqueous solution, will collapse into a globule as evidenced by a coarge-grain computer simulation. Color code: Backbone (dark blue), Aromatic side chains (light blue). |
A single-chain collapsed into a micellar structure with the hydrophobic groups (yellow) partially buried in the interior, and the polar groups (red & blue) on the surface. |
• Coarse-grain peptoid model: MF-CG-TOID-MC is software to initialize, simulate, and analyze Monte Carlo simulations of the Molecular Foundry Coarse-grained Model for Peptoids (MF-CG-TOID). Software available here, as described in reference #8 below.
• Atomistic CHARMM peptoid model: MFTOID is a set of forcefields for CHARMM that have been customized for use with peptoids, as decribed in Mirijanian, D., et al., J. Comp. Chem. (2014).
CHARMM files: Parameter file (inp file); Topology file (inp file)
Build your own nanosheet model:
Dr. Ryan Spencer (UC Irvine) created a nanosheet creation tool which allows you to rapidly build a molecular model of multple peptoid chains assembled into a nanosheet bilayer. The program will export your model as a .pdb file, which you can view in PyMol or another molecular viewer. Check out the nanosheet builder program & tutorial here.
Nanosheet formation mechanism:
In progress!
Recent review articles on peptoids:
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Sequence Programmable Peptoid Polymers for Diverse Materials Applications. |
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Precision sequence control in bioinspired peptoid polymers. Sun, J.; Proulx, C.; Zuckermann, R.N., In Sequence-Controlled Polymers: Synthesis, Self-Assembly, and Properties; ACS Symposium Series, Francois-Lutz, J., Ed. 1170, 25-53 (2014). http://pubs.acs.org/doi/abs/10.1021/bk-2014-1170.ch003 |
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Peptoid Polymers: A Highly Designable Bioinspired Material. |
Peptoid nanosheet papers:
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Molecular Engineering of the Peptoid Nanosheet Hydrophobic Core. |
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Structure–Rheology Relationship in Nanosheet-Forming Peptoid Monolayers. Robertson, E.J.; Nehls, E.M.; Zuckermann, R.N., Langmuir, 32, 12146-12158 (2016). http://pubs.acs.org/doi/abs/10.1021/acs.langmuir.6b02736 Supporting Info (pdf) |
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Improved chemical and mechanical stability of peptoid nanosheets by photo-crosslinking the hydrophobic core. Flood, D.; Proulx, C.; Robertson, E.J.; Battigelli, A.; Wang, S.; Schwartzberg, A.M.; Zuckermann, R.N., Chem. Commun., 52, 4753-4756 (2016). http://pubs.rsc.org/EN/content/articlelanding/2016/cc/c6cc00588h Supporting Info (pdf) |
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Design, Synthesis, Assembly, and Engineering of Peptoid Nanosheets. Robertson, E.J.; Battigelli, A.; Proulx, C.; Mannige, R.V.; Haxton, T.K.; Yun, L.; Whitelam, S.; Zuckermann, R.N., Accounts of Chemical Research, ASAP online (2016). http://pubs.acs.org/doi/abs/10.1021/acs.accounts.5b00439 |
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Peptoid nanosheets exhibit a new secondary-structure motif. |
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Peptoid nanosheets as soluble, two-dimensional templates for calcium carbonate mineralization. |
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Modeling Sequence-Specific Polymers Using Anisotropic Coarse-Grained Sites Allows Quantitative Comparison with Experiment. |
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Structure-Determining Step in the Hierarchical Assembly of Peptoid Nanosheets. |
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Assembly and molecular order of two-dimensional peptoid nanosheets through the oil–water interface. |
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Antibody-Mimetic Peptoid Nanosheets for Molecular Recognition. |
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Solid-phase Submonomer Synthesis of Peptoid Polymers and their Self-Assembly into Highly-Ordered Nanosheets. |
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Shaken, not stirred: Collapsing a peptoid monolayer to produce free-floating, stable nanosheets. |
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Folding of a Single-Chain, Information-Rich Polypeptoid Sequence into a Highly-Ordered Nanosheet. |
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Free-floating ultra-thin two-dimensional crystals from sequence-specific peptoid polymers. |
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