Polymorphism in Self-Assembly of Short Peptoid Sequences

Zheng, Renyu; Zhao, Mingfei; Zhou, Wenhao; Trinh, Thi Kim Hoang; Zhang, Shuai; De Yoreo, James J.; Ferguson, Andrew L.; Chen, Chun-Long

doi:10.1021/polymscitech.5c00123

Polymorphism in Self-Assembly of Short Peptoid Sequences

Journal Article · Fri Jan 30 00:00:00 EST 2026 · Polymer Science and Technology

DOI:https://doi.org/10.1021/polymscitech.5c00123· OSTI ID:3024411

Zheng, Renyu ^[1]; ^[2]; ^[3]; ^[4]; ^[3]; ^[3]; ^[5]; ^[1]

Univ. of Washington, Seattle, WA (United States); Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Univ. of Alabama, Birmingham, AL (United States)
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Univ. of Washington, Seattle, WA (United States)
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Univ. of Chicago, IL (United States)

Due to various applications enabled by diverse morphologies of self-assembled sequence-defined polymers, controlling the self-assembly of synthetic peptidomimetics into designed morphologies has emerged as a promising route for the development of bioinspired functional materials. Herein, we report morphological control over the assembly of a series of short peptoids, or poly-N-substituted glycines, that contain asymmetric hydrophobic domains. We demonstrate that the inherent flexibility of amphiphilic peptoid bilayers drives assembly polymorphism, resulting in the coexistence of nanosheets, twisted ribbons, and nanofibers three distinct morphologies. By tuning peptoid molecular interactions through variations in sequence design, solution pH, and temperature, we demonstrate precise control over the twisting and folding of peptoid bilayers, enabling the formation of well-defined nanosheets and nanohelices. Molecular dynamics simulations further unravel how the introduction of asymmetric hydrophobic domains enables the flexibility of peptoid bilayers and results in peptoid assembly polymorphism. By tuning peptoid molecular interactions through heating, we further demonstrate the transformation of nanosheets into nanohelices. We envision that our mechanistic investigation of peptoid assembly polymorphism provides a strong foundation for leveraging peptoid sequences and chemistries to achieve controlled molecular interactions, driving the creation of biomimetic materials with tailored morphologies and functionalities.

View Accepted Manuscript (DOE)

Research Organization:: Univ. of Washington, Seattle, WA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-05CH11231; AC05-76RL01830; SC0019288

OSTI ID:: 3024411

Alternate ID(s):: OSTI ID: 3024094

Journal Information:: Polymer Science and Technology, Journal Name: Polymer Science and Technology Journal Issue: 3 Vol. 2; ISSN 2997-3279

Publisher:: ACS PublicationsCopyright Statement

Country of Publication:: United States

Language:: English

References (63)

Self-Repair and Patterning of 2D Membrane-Like Peptoid Materials Jiao, Fang; Chen, Yulin; Jin, Haibao Advanced Functional Materials, Vol. 26, Issue 48 https://doi.org/10.1002/adfm.201602365	journal	August 2016
Polymorphic Self‐Assembly with Procedural Flexibility for Monodisperse Quaternary Protein Structures of DegQ Enzymes Jeon, Hanul; Han, Ah‐reum; Oh, Sangmin Advanced Materials, Vol. 36, Issue 19 https://doi.org/10.1002/adma.202308837	journal	February 2024
[Co2(ppca)2(H2O)(V4O12)0.5]: A Framework Material Exhibiting Reversible Shrinkage and Expansion through a Single-Crystal-to-Single-Crystal Transformation Involving a Change in the Cobalt Coordination Environment Chen, Chun-Long; Goforth, Andrea M.; Smith, Mark D. Angewandte Chemie International Edition, Vol. 44, Issue 41 https://doi.org/10.1002/anie.200502309	journal	October 2005
Peptide-Based Methods for the Preparation of Nanostructured Inorganic Materials Chen, Chun-Long; Rosi, Nathaniel L. Angewandte Chemie International Edition, Vol. 49, Issue 11, p. 1924-1942 https://doi.org/10.1002/anie.200903572	journal	February 2010
Amyloid Polymorphism in the Protein Folding and Aggregation Energy Landscape Adamcik, Jozef; Mezzenga, Raffaele Angewandte Chemie International Edition, Vol. 57, Issue 28 https://doi.org/10.1002/anie.201713416	journal	June 2018
Hierarchical Self‐Assembly of Multidimensional Functional Materials from Sequence‐Defined Peptoids Shao, Li; Hu, Dehong; Zheng, Shao‐Liang Angewandte Chemie International Edition, Vol. 63, Issue 24 https://doi.org/10.1002/anie.202403263	journal	May 2024
GROMACS: Fast, flexible, and free Van Der Spoel, David; Lindahl, Erik; Hess, Berk Journal of Computational Chemistry, Vol. 26, Issue 16 https://doi.org/10.1002/jcc.20291	journal	January 2005
Amphiphilic Peptoid‐Directed Assembly of Oligoanilines into Highly Crystalline Conducting Nanotubes Li, Zhiliang; Tran, Duyen K.; Nguyen, Mary Macromolecular Rapid Communications, Vol. 43, Issue 4 https://doi.org/10.1002/marc.202100639	journal	January 2022
Bioinspired Peptoid Nanotubes for Targeted Tumor Cell Imaging and Chemo‐Photodynamic Therapy Luo, Yanan; Song, Yang; Wang, Mingming Small, Vol. 15, Issue 43 https://doi.org/10.1002/smll.201902485	journal	August 2019
Co‐Assembly of Carbon Nanotube Porins into Biomimetic Peptoid Membranes Zhang, Shuai; Hettige, Jeevapani J.; Li, Yuhao Small, Vol. 19, Issue 21 https://doi.org/10.1002/smll.202206810	journal	February 2023
Assembly of highly efficient aqueous light-harvesting system from sequence-defined peptoids for cytosolic microRNA detection Song, Yang; Cai, Xiaoli; Wang, Mingming Nano Research, Vol. 17, Issue 2 https://doi.org/10.1007/s12274-023-6008-0	journal	August 2023
Elastic moduli of lipid membranes: Reproducibility of AFM measures Eid, Jad; Greige-Gerges, Hélène; Monticelli, Luca Chemistry and Physics of Lipids, Vol. 234 https://doi.org/10.1016/j.chemphyslip.2020.105011	journal	January 2021
2D nanomaterials assembled from sequence-defined molecules Mu, Peng; Zhou, Guangwen; Chen, Chun-Long Nano-Structures & Nano-Objects, Vol. 15 https://doi.org/10.1016/j.nanoso.2017.09.010	journal	July 2018
Constructing bioactive peptides with pH-dependent activities Tu, Zhigang; Volk, Melanie; Shah, Khushali Peptides, Vol. 30, Issue 8 https://doi.org/10.1016/j.peptides.2009.05.009	journal	August 2009
GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers Abraham, Mark James; Murtola, Teemu; Schulz, Roland SoftwareX, Vol. 1-2 https://doi.org/10.1016/j.softx.2015.06.001	journal	September 2015
Programming Amphiphilic Peptoid Oligomers for Hierarchical Assembly and Inorganic Crystallization Cai, Bin; Li, Zhiliang; Chen, Chun-Long Accounts of Chemical Research, Vol. 54, Issue 1 https://doi.org/10.1021/acs.accounts.0c00533	journal	November 2020
Design, Synthesis, Assembly, and Engineering of Peptoid Nanosheets Robertson, Ellen J.; Battigelli, Alessia; Proulx, Caroline Accounts of Chemical Research, Vol. 49, Issue 3 https://doi.org/10.1021/acs.accounts.5b00439	journal	January 2016
Hierarchical Self-Assembly Pathways of Peptoid Helices and Sheets Zhao, Mingfei; Lachowski, Kacper J.; Zhang, Shuai Biomacromolecules, Vol. 23, Issue 3 https://doi.org/10.1021/acs.biomac.1c01385	journal	January 2022
Computational and Experimental Determination of the Properties, Structure, and Stability of Peptoid Nanosheets and Nanotubes Zhao, Mingfei; Zhang, Shuai; Zheng, Renyu Biomacromolecules, Vol. 24, Issue 6 https://doi.org/10.1021/acs.biomac.3c00107	journal	May 2023
Designing Sequence-Defined Peptoids for Biomimetic Control over Inorganic Crystallization Yang, Wenchao; Yin, Qiuxiang; Chen, Chun-Long Chemistry of Materials, Vol. 33, Issue 9 https://doi.org/10.1021/acs.chemmater.1c00243	journal	April 2021
Hierarchical Nanomaterials Assembled from Peptoids and Other Sequence-Defined Synthetic Polymers Li, Zhiliang; Cai, Bin; Yang, Wenchao Chemical Reviews, Vol. 121, Issue 22 https://doi.org/10.1021/acs.chemrev.1c00024	journal	August 2021
Protein Assembly by Design Zhu, Jie; Avakyan, Nicole; Kakkis, Albert Chemical Reviews, Vol. 121, Issue 22 https://doi.org/10.1021/acs.chemrev.1c00308	journal	August 2021
Hierarchical Materials from High Information Content Macromolecular Building Blocks: Construction, Dynamic Interventions, and Prediction Shao, Li; Ma, Jinrong; Prelesnik, Jesse L. Chemical Reviews, Vol. 122, Issue 24 https://doi.org/10.1021/acs.chemrev.2c00220	journal	October 2022
Peptoids and Polypeptoids at the Frontier of Supra- and Macromolecular Engineering Gangloff, Niklas; Ulbricht, Juliane; Lorson, Thomas Chemical Reviews, Vol. 116, Issue 4 https://doi.org/10.1021/acs.chemrev.5b00201	journal	December 2015
Importance of the Positively Charged σ-Hole in Crystal Engineering of Halogenated Polypeptoids Seidler, Morgan; Li, Nan K.; Luo, Xubo The Journal of Physical Chemistry B, Vol. 126, Issue 22 https://doi.org/10.1021/acs.jpcb.2c01843	journal	May 2022
Early-Stage Aggregation and Crystalline Interactions of Peptoid Nanomembranes Hammons, Joshua A.; Baer, Marcel D.; Jian, Tengyue The Journal of Physical Chemistry Letters, Vol. 12, Issue 26 https://doi.org/10.1021/acs.jpclett.1c01033	journal	June 2021
Nanoparticle-Mediated Assembly of Peptoid Nanosheets Functionalized with Solid-Binding Proteins: Designing Heterostructures for Hierarchy Ma, Jinrong; Cai, Bin; Zhang, Shuai Nano Letters, Vol. 21, Issue 4 https://doi.org/10.1021/acs.nanolett.0c04285	journal	February 2021
Peptoid-Based Programmable 2D Nanomaterial Sensor for Selective and Sensitive Detection of H ₂ S in Live Cells Wang, Mingming; Song, Yang; Mu, Peng ACS Applied Bio Materials, Vol. 3, Issue 9 https://doi.org/10.1021/acsabm.0c00657	journal	August 2020
Designed Metal-Containing Peptoid Membranes as Enzyme Mimetics for Catalytic Organophosphate Degradation Trinh, Thi Kim Hoang; Jian, Tengyue; Jin, Biao ACS Applied Materials & Interfaces, Vol. 15, Issue 44 https://doi.org/10.1021/acsami.3c11816	journal	October 2023
Assembly of Metalloporphyrin Peptoids into Crystalline Nanomaterials as a Multifunctional System for Biomimetic Catalysis and Sensing Trinh, Thi Kim Hoang; Jin, Biao; Zuckermann, Ronald N. ACS Applied Materials & Interfaces https://doi.org/10.1021/acsami.5c05546	journal	July 2025
Atomic-Scale Corrugations in Crystalline Polypeptoid Nanosheets Revealed by Three-Dimensional Cryogenic Electron Microscopy Jiang, Xi; Seidler, Morgan; Butterfoss, Glenn L. ACS Macro Letters, Vol. 12, Issue 5 https://doi.org/10.1021/acsmacrolett.3c00101	journal	April 2023
Self-Assembly of Minimal Peptoid Sequences Castelletto, Valeria; Seitsonen, Jani; Tewari, Kunal M. ACS Macro Letters, Vol. 9, Issue 4 https://doi.org/10.1021/acsmacrolett.9b01010	journal	March 2020
Highly Bright and Photostable Two-Dimensional Nanomaterials Assembled from Sequence-Defined Peptoids Song, Yang; Wang, Mingming; Akkineni, Susrut ACS Materials Letters, Vol. 3, Issue 4 https://doi.org/10.1021/acsmaterialslett.1c00110	journal	March 2021
Hierarchical Approach for Controlled Assembly of Branched Nanostructures from One Polymer Compound by Engineering Crystalline Domains Ding, Xiangmin; Liu, Dandan; Jiang, Xi ACS Nano, Vol. 16, Issue 7 https://doi.org/10.1021/acsnano.2c01171	journal	May 2022
Discovery of Stable and Selective Antibody Mimetics from Combinatorial Libraries of Polyvalent, Loop-Functionalized Peptoid Nanosheets Kim, Jae Hong; Kim, Samuel C.; Kline, Mark A. ACS Nano https://doi.org/10.1021/acsnano.9b07498	journal	December 2019
Biomimetic CaCO ₃ Mineralization using Designer Molecules and Interfaces Sommerdijk, Nico A. J. M.; With, Gijsbertus de Chemical Reviews, Vol. 108, Issue 11 https://doi.org/10.1021/cr078259o	journal	November 2008
Protein- and Peptide-Directed Syntheses of Inorganic Materials Dickerson, Matthew B.; Sandhage, Kenneth H.; Naik, Rajesh R. Chemical Reviews, Vol. 108, Issue 11, p. 4935-4978 https://doi.org/10.1021/cr8002328	journal	November 2008
Controlling Mineral Morphologies and Structures in Biological and Synthetic Systems Meldrum, Fiona C.; Cölfen, Helmut Chemical Reviews, Vol. 108, Issue 11 https://doi.org/10.1021/cr8002856	journal	November 2008
Multidimensional Frameworks Assembled from Silver(I) Coordination Polymers Containing Flexible Bis(thioquinolyl) Ligands: Role of the Intra- and Intermolecular Aromatic Stacking Interactions Chen, Chun-Long; Su, Cheng-Yong; Cai, Yue-Peng Inorganic Chemistry, Vol. 42, Issue 12 https://doi.org/10.1021/ic0341035	journal	June 2003
Disilver(I) Rectangular-Shaped Metallacycles: X-ray Crystal Structure and Dynamic Behavior in Solution Chen, Chun-Long; Tan, Hai-Yan; Yao, Jun-Hua Inorganic Chemistry, Vol. 44, Issue 23 https://doi.org/10.1021/ic050673o	journal	October 2005
Hierarchical Self-Assembly of a Biomimetic Diblock Copolypeptoid into Homochiral Superhelices Murnen, Hannah K.; Rosales, Adrianne M.; Jaworski, Jonathan N. Journal of the American Chemical Society, Vol. 132, Issue 45 https://doi.org/10.1021/ja106340f	journal	November 2010
Guest Inclusion and Structural Dynamics in 2-D Hydrogen-Bonded Metal−Organic Frameworks Chen, Chun-Long; Beatty, Alicia M. Journal of the American Chemical Society, Vol. 130, Issue 51 https://doi.org/10.1021/ja806180z	journal	December 2008
Selective Synthesis of Lysine Peptides and the Prebiotically Plausible Synthesis of Catalytically Active Diaminopropionic Acid Peptide Nitriles in Water Thoma, Benjamin; Powner, Matthew W. Journal of the American Chemical Society, Vol. 145, Issue 5 https://doi.org/10.1021/jacs.2c12497	journal	January 2023
Crystalline Peptoid Nanofibers with a Single-Unit Cell Cross Section Lee, Yen Jea; Seidler, Morgan; Luo, Xubo Journal of the American Chemical Society, Vol. 147, Issue 31 https://doi.org/10.1021/jacs.5c03996	journal	June 2025
Universal Relationship between Molecular Structure and Crystal Structure in Peptoid Polymers and Prevalence of the cis Backbone Conformation Greer, Douglas R.; Stolberg, Michael A.; Kundu, Joyjit Journal of the American Chemical Society, Vol. 140, Issue 2 https://doi.org/10.1021/jacs.7b11891	journal	January 2018
Peptoid Polymers: A Highly Designable Bioinspired Material Sun, Jing; Zuckermann, Ronald N. ACS Nano, Vol. 7, Issue 6 https://doi.org/10.1021/nn4015714	journal	May 2013
The coming of age of de novo protein design Huang, Po-Ssu; Boyken, Scott E.; Baker, David Nature, Vol. 537, Issue 7620 https://doi.org/10.1038/nature19946	journal	September 2016
Highly stable and self-repairing membrane-mimetic 2D nanomaterials assembled from lipid-like peptoids Jin, Haibao; Jiao, Fang; Daily, Michael D. Nature Communications, Vol. 7, Issue 1 https://doi.org/10.1038/ncomms12252	journal	July 2016
Designable and dynamic single-walled stiff nanotubes assembled from sequence-defined peptoids Jin, Haibao; Ding, Yan-Huai; Wang, Mingming Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-017-02059-1	journal	January 2018
Highly stable and tunable peptoid/hemin enzymatic mimetics with natural peroxidase-like activities Jian, Tengyue; Zhou, Yicheng; Wang, Peipei Nature Communications, Vol. 13, Issue 1 https://doi.org/10.1038/s41467-022-30285-9	journal	May 2022
Assembly of short amphiphilic peptoids into nanohelices with controllable supramolecular chirality Zheng, Renyu; Zhao, Mingfei; Du, Jingshan S. Nature Communications, Vol. 15, Issue 1 https://doi.org/10.1038/s41467-024-46839-y	journal	April 2024
Assembled peptoid crystalline nanomaterials as carbonic anhydrase mimics for promoted hydration and sequestration of CO2 Chakma, Progyateg; Chen, Ying; Harris, Bradley S. Nature Communications, Vol. 16, Issue 1 https://doi.org/10.1038/s41467-025-62366-w	journal	August 2025
Biomimetic peptide self-assembly for functional materials Levin, Aviad; Hakala, Tuuli A.; Schnaider, Lee Nature Reviews Chemistry, Vol. 4, Issue 11 https://doi.org/10.1038/s41570-020-0215-y	journal	September 2020
Local structural flexibility drives oligomorphism in computationally designed protein assemblies Khmelinskaia, Alena; Bethel, Neville P.; Fatehi, Farzad Nature Structural & Molecular Biology, Vol. 32, Issue 6 https://doi.org/10.1038/s41594-025-01490-z	journal	February 2025
Stimuli responsive dynamic transformations in supramolecular gels Panja, Santanu; Adams, Dave J. Chemical Society Reviews, Vol. 50, Issue 8 https://doi.org/10.1039/D0CS01166E	journal	January 2021
Tuning the mechanical flexibility of organic molecular crystals by polymorphism for flexible optical waveguides Feiler, Torvid; Bhattacharya, Biswajit; Michalchuk, Adam A. L. CrystEngComm, Vol. 23, Issue 34 https://doi.org/10.1039/D1CE00642H	journal	January 2021
Crystallization and self-assembly of shape-complementary sequence-defined peptoids Xuan, Sunting; Jiang, Xi; Balsara, Nitash P. Polymer Chemistry, Vol. 12, Issue 33 https://doi.org/10.1039/D1PY00426C	journal	January 2021
A non-interpenetrating 2D coordination polymer from a (CH2)8 spacer-based highly flexible linear ligand and AgCF3CO2Electronic supplementary information (ESI) available: 1H NMR spectra and data for C8TQ and complex 1 and the 3-D structure of complex 1. See http://www.rsc.org/suppdata/nj/b3/b301777j Chen, Chun-Long; Su, Cheng-Yong; Cai, Yue-Peng New Journal of Chemistry, Vol. 27, Issue 5 https://doi.org/10.1039/b301777j	journal	April 2003
Atomic-level engineering and imaging of polypeptoid crystal lattices Xuan, Sunting; Jiang, Xi; Spencer, Ryan K. Proceedings of the National Academy of Sciences, Vol. 116, Issue 45 https://doi.org/10.1073/pnas.1909992116	journal	October 2019
Hierarchical supramolecular assembly of a single peptoid polymer into a planar nanobrush with two distinct molecular packing motifs Sun, Jing; Wang, Zhiwei; Zhu, Chenhui Proceedings of the National Academy of Sciences, Vol. 117, Issue 50 https://doi.org/10.1073/pnas.2011816117	journal	December 2020
Polymorphism in tubulin assemblies: A mechanical model García-Aguilar, Ireth; Zwaan, Steven; Giomi, Luca Physical Review Research, Vol. 5, Issue 2 https://doi.org/10.1103/PhysRevResearch.5.023093	journal	May 2023
Programmable two-dimensional nanocrystals assembled from POSS-containing peptoids as efficient artificial light-harvesting systems Wang, Mingming; Song, Yang; Zhang, Shuai Science Advances, Vol. 7, Issue 20 https://doi.org/10.1126/sciadv.abg1448	journal	May 2021
The Protein Folding Problem Dill, Ken A.; Ozkan, S. Banu; Shell, M. Scott Annual Review of Biophysics, Vol. 37, Issue 1 https://doi.org/10.1146/annurev.biophys.37.092707.153558	journal	June 2008

Similar Records

Assembly of short amphiphilic peptoids into nanohelices with controllable supramolecular chirality

Journal Article · Mon Apr 15 20:00:00 EDT 2024 · Nature Communications · OSTI ID:2337750

Related Subjects

assembly polymorphism
biomimetic materials
morphological control
peptoids
sequence-defined polymers

Polymorphism in Self-Assembly of Short Peptoid Sequences

Citation Formats

References (63)

Similar Records

Related Subjects