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Title: Computational and Experimental Determination of the Properties, Structure, and Stability of Peptoid Nanosheets and Nanotubes

Journal Article · · Biomacromolecules
ORCiD logo [1]; ORCiD logo [2];  [2]; ORCiD logo [3]; ORCiD logo [4]; ORCiD logo [2]; ORCiD logo [3]; ORCiD logo [4]; ORCiD logo [4]; ORCiD logo [1]
  1. University of Chicago, IL (United States)
  2. University of Washington, Seattle, WA (United States); Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
  3. University of Washington, Seattle, WA (United States)
  4. Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); University of Washington, Seattle, WA (United States)

Peptoids (N-substituted glycines) are a group of highly controllable peptidomimetic polymers. Amphiphilic diblock peptoids have been engineered to assemble crystalline nanospheres, nanofibrils, nanosheets, and nanotubes with biochemical, biomedical, and bioengineering applications. The mechanical properties of peptoid nanoaggregates and their relationship to the emergent self-assembled morphologies have been relatively unexplored and are critical for the rational design of peptoid nanomaterials. In this work, we consider a family of amphiphilic diblock peptoids consisting of a prototypical tube-former (Nbrpm6Nc6, a NH2-capped hydrophobic block of six N-((4-bromophenyl)methyl)glycine residues conjugated to a polar NH3(CH2)5CO tail), a prototypical sheet-former (Nbrpe6Nc6, where the hydrophobic block comprises six N-((4-bromophenyl)ethyl)glycine residues), and an intermediate sequence that forms mixed structures ((NbrpeNbrpm)3Nc6). We combine all-atom molecular dynamics simulations and atomic force microscopy to determine the mechanical properties of the self-assembled 2D crystalline nanosheets and relate these properties to the observed self-assembled morphologies. We find good agreement between our computational predictions and experimental measurements of Young’s modulus of crystalline nanosheets. A computational analysis of the bending modulus along the two axes of the planar crystalline nanosheets reveals bending to be more favorable along the axis in which the peptoids stack by interdigitation of the side chains compared to that in which they form columnar crystals with π-stacked side chains. Here, we construct molecular models of nanotubes of the Nbrpm6Nc6 tube-forming peptoid and predict a stability optimum in good agreement with experimental measurements. A theoretical model of nanotube stability suggests that this optimum is a free energy minimum corresponding to a “Goldilocks” tube radius at which capillary wave fluctuations in the tube wall are minimized.

Research Organization:
Univ. of Washington, Seattle, WA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Science Foundation (NSF)
Grant/Contract Number:
SC0019288; DGE-1762114; DMR-1828629
OSTI ID:
1993122
Journal Information:
Biomacromolecules, Vol. 24, Issue 6; ISSN 1525-7797
Publisher:
American Chemical SocietyCopyright Statement
Country of Publication:
United States
Language:
English

References (84)

Pressure-induced hard-to-soft transition of a single carbon nanotube journal October 2004
Tackling Exascale Software Challenges in Molecular Dynamics Simulations with GROMACS book January 2015
Nanoindentation models and Young's modulus of monolayer graphene: A molecular dynamics study journal February 2013
Poisson's ratio and modern materials journal October 2011
Peptoid-directed assembly of CdSe nanoparticles journal January 2021
Impact of Helical Chain Shape in Sequence-Defined Polymers on Polypeptoid Block Copolymer Self-Assembly journal February 2018
Molecular modeling studies of peptoid polymers journal January 2017
Development and use of an atomistic CHARMM-based forcefield for peptoid simulation journal November 2013
Dynamics of thermally driven capillary waves for two-dimensional droplets journal May 2010
Information Theory and an Extension of the Maximum Likelihood Principle book January 1998
Self-assembly of crystalline nanotubes from monodisperse amphiphilic diblock copolypeptoid tiles journal March 2016
Molecular dynamics analysis of temperature effects on nanoindentation measurement journal September 2003
Comparison of the proteolytic susceptibilities of homologous L-amino acid, D-amino acid, and N-substituted glycine peptide and peptoid oligomers journal May 1995
A CGenFF‐based force field for simulations of peptoids with both cis and trans peptide bonds journal May 2019
Universal Relationship between Molecular Structure and Crystal Structure in Peptoid Polymers and Prevalence of the cis Backbone Conformation journal January 2018
Exploring the sequence space for (tri-)peptide self-assembly to design and discover new hydrogels journal December 2014
Small Molecular Antibacterial Peptoid Mimics: The Simpler the Better! journal February 2014
Peptoids: Bio-Inspired Polymers as Potential Pharmaceuticals journal August 2011
Indentation Versus Tensile Measurements of Young's Modulus for Soft Biological Tissues journal June 2011
Guiding principles for peptide nanotechnology through directed discovery journal January 2018
Hierarchical Materials from High Information Content Macromolecular Building Blocks: Construction, Dynamic Interventions, and Prediction journal October 2022
Imaging Unstained Synthetic Polymer Crystals and Defects on Atomic Length Scales Using Cryogenic Electron Microscopy journal September 2018
Wet Nanoindentation of the Solid Electrolyte Interphase on Thin Film Si Electrodes journal October 2015
Comparison of simple potential functions for simulating liquid water journal July 1983
Uniform, Large-Area, Highly Ordered Peptoid Monolayer and Bilayer Films for Sensing Applications journal September 2019
Peptoid origins journal December 2010
Potent and selective photo-inactivation of proteins with peptoid-ruthenium conjugates journal March 2010
Control of Crystallization and Melting Behavior in Sequence Specific Polypeptoids journal July 2010
Peptoid nanotubes: an oligomer macrocycle that reversibly sequesters water via single-crystal-to-single-crystal transformations journal January 2013
GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers journal September 2015
Determination of Line Tension in Lipid Monolayers by Fourier Analysis of Capillary Waves journal September 2007
The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: Peptoid molecular transporters journal November 2000
Bioinspired Peptoid Nanotubes for Targeted Tumor Cell Imaging and Chemo‐Photodynamic Therapy journal August 2019
Design, Synthesis, Assembly, and Engineering of Peptoid Nanosheets journal January 2016
Solvent Effects on the Self-Assembly of an Amphiphilic Polypeptide Incorporating α-Helical Hydrophobic Blocks journal December 2020
Sequence-Defined Nanotubes Assembled from IR780-Conjugated Peptoids for Chemophototherapy of Malignant Glioma journal January 2021
Elastic Properties of a Single Lamella of Montmorillonite by Molecular Dynamics Simulation journal December 2003
Self-Assembly of Minimal Peptoid Sequences journal March 2020
Peptoid nanosheets exhibit a new secondary-structure motif journal October 2015
PEPDROID: Development of a Generic DREIDING-Based Force Field for the Assessment of Peptoid Secondary Structures journal September 2018
A unified formulation of the constant temperature molecular dynamics methods journal July 1984
Free-floating ultrathin two-dimensional crystals from sequence-specific peptoid polymers journal April 2010
SciPy 1.0: fundamental algorithms for scientific computing in Python journal February 2020
Amphiphilic Peptoid‐Directed Assembly of Oligoanilines into Highly Crystalline Conducting Nanotubes journal January 2022
Determining the bending modulus of a lipid membrane by simulating buckling journal June 2013
Hierarchical Nanomaterials Assembled from Peptoids and Other Sequence-Defined Synthetic Polymers journal August 2021
Exploring the links between peptoid antibacterial activity and toxicity journal January 2017
Click to Fit:  Versatile Polyvalent Display on a Peptidomimetic Scaffold journal April 2005
Atomic-level engineering and imaging of polypeptoid crystal lattices journal October 2019
Canonical sampling through velocity rescaling journal January 2007
Peptoid Polymers: A Highly Designable Bioinspired Material journal May 2013
Highly stable and self-repairing membrane-mimetic 2D nanomaterials assembled from lipid-like peptoids journal July 2016
Extending the treatment of backbone energetics in protein force fields: Limitations of gas-phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations journal August 2004
Reactive Potentials for Advanced Atomistic Simulations journal July 2013
LINCS: A linear constraint solver for molecular simulations journal September 1997
Designable and dynamic single-walled stiff nanotubes assembled from sequence-defined peptoids journal January 2018
Molecular dynamics with coupling to an external bath journal October 1984
On Calculating the Bending Modulus of Lipid Bilayer Membranes from Buckling Simulations journal June 2020
Optimization of the Additive CHARMM All-Atom Protein Force Field Targeting Improved Sampling of the Backbone ϕ, ψ and Side-Chain χ 1 and χ 2 Dihedral Angles journal August 2012
Nanoparticle-Mediated Assembly of Peptoid Nanosheets Functionalized with Solid-Binding Proteins: Designing Heterostructures for Hierarchy journal February 2021
A molecular dynamics study of Young’s modulus of multilayer graphene journal May 2019
Tunable peptoid microspheres: effects of side chain chemistry and sequence journal January 2013
Hierarchical Self-Assembly of a Biomimetic Diblock Copolypeptoid into Homochiral Superhelices journal November 2010
Efficient method for the preparation of peptoids [oligo(N-substituted glycines)] by submonomer solid-phase synthesis journal December 1992
Shaken, Not Stirred: Collapsing a Peptoid Monolayer To Produce Free-Floating, Stable Nanosheets journal December 2011
Hierarchical Self-Assembly Pathways of Peptoid Helices and Sheets journal January 2022
A combinatorial approach to the discovery of efficient cationic peptoid reagents for gene delivery journal February 1998
Polymorphic transitions in single crystals: A new molecular dynamics method journal December 1981
Molecular dynamics simulation of nanoindentation of Fe3C and Fe4C journal March 2014
Capillary force induced structural deformation in liquid infiltrated elastic circular tubes journal June 2010
Efficient Cytosolic Delivery Using Crystalline Nanoflowers Assembled from Fluorinated Peptoids journal November 2018
PACKMOL: A package for building initial configurations for molecular dynamics simulations journal October 2009
Recent development and application of constant pH molecular dynamics journal May 2014
Molecular dynamics simulations on nanoindentation mechanisms of multilayered films journal October 2008
Hertz model or Oliver & Pharr analysis? Tutorial regarding AFM nanoindentation experiments on biological samples journal March 2020
Sequence Programmable Peptoid Polymers for Diverse Materials Applications journal April 2015
Controlled synthesis of highly-branched plasmonic gold nanoparticles through peptoid engineering journal June 2018
Avogadro: an advanced semantic chemical editor, visualization, and analysis platform journal August 2012
A smooth particle mesh Ewald method journal November 1995
Molecular Engineering of the Peptoid Nanosheet Hydrophobic Core journal October 2016
VMD: Visual molecular dynamics journal February 1996
Self-assembling peptide and protein amyloids: from structure to tailored function in nanotechnology journal January 2017
Curvature Softening and Negative Compressibility of Gel-Phase Lipid Membranes journal October 2015
2D nanomaterials assembled from sequence-defined molecules journal July 2018