Stability of Nanopeptides: Structure and Molecular Exchange of Self-assembled Peptide Fibers

Nico König; Szymon Mikolaj Szostak; Josefine Eilsø Nielsen; Martha Dunbar; Su Yang; Weike Chen; Ari Benjamin; Aurel Radulescu; Najet Mahmoudi; Lutz Willner; Sinan Keten; He Dong; Reidar Lund

doi:10.1021/acsnano.3c01811

Stability of Nanopeptides: Structure and Molecular Exchange of Self-assembled Peptide Fibers

Nico König, Szymon Mikolaj Szostak, Josefine Eilsø Nielsen, Martha Dunbar, Su Yang, Weike Chen, Ari Benjamin, Aurel Radulescu, Najet Mahmoudi, Lutz Willner, Sinan Keten, He Dong, Reidar Lund^*

^*Corresponding author for this work

Mechanical Engineering

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Often nanostructures formed by self-assembly of small molecules based on hydrophobic interactions are rather unstable, causing morphological changes or even dissolution when exposed to changes in aqueous media. In contrast, peptides offer precise control of the nanostructure through a range of molecular interactions where physical stability can be engineered in and, to a certain extent, decoupled from size via rational design. Here, we investigate a family of peptides that form beta-sheet nanofibers and demonstrate a remarkable physical stability even after attachment of poly(ethylene glycol). We employed small-angle neutron/X-ray scattering, circular dichroism spectroscopy, and molecular dynamics simulation techniques to investigate the detailed nanostructure, stability, and molecular exchange. The results for the most stable sequence did not reveal any structural alterations or unimer exchange for temperatures up to 85 °C in the biologically relevant pH range. Only under severe mechanical perturbation (i.e., tip sonication) would the fibers break up, which is reflected in a very high activation barrier for unimer exchange of ∼320 kJ/mol extracted from simulations. The results give important insight into the relation between molecular structure and stability of peptide nanostructure that is important for, e.g., biomedical applications.

Original language	English (US)
Pages (from-to)	12394-12408
Number of pages	15
Journal	ACS nano
Volume	17
Issue number	13
DOIs	https://doi.org/10.1021/acsnano.3c01811
State	Published - Jul 11 2023

Funding

We gratefully acknowledge NordForsk (Project No. 82004, JEN and RL) and the Norwegian Research Council (Project No. 315666, RL). This work was supported by the U.S. National Science Foundation (Award: DMR-1824614 to HD and SY). S.K. acknowledges the support from an ONR Director of Research Early Career Award (PECASE, award no. N00014163175).We kindly acknowledge provision of SAXS beamtime at BM29 at ESRF (Grenoble, France) and thank Dr. Mark Tully and the PSCM lab for support during the SAXS experiment. We also acknowledge the Norwegian national infrastructure for X-ray diffraction and scattering (RECX) at the University of Oslo (Norway) for SAXS beamtime, as well as SANS beamtime at KWS-2 at MLZ (Garching, Germany) and Sans2d at ISIS (Didcot, United Kingdom) where we received additional help from Dr. Leide Cavalcanti. Furthermore, we acknowledge support from a supercomputing grant from Northwestern University High Performance Computing Center. We gratefully acknowledge NordForsk (Project No. 82004, JEN and RL) and the Norwegian Research Council (Project No. 315666, RL). This work was supported by the U.S. National Science Foundation (Award: DMR-1824614 to HD and SY). S.K. acknowledges the support from an ONR Director of Research Early Career Award (PECASE, award no. N00014163175).We kindly acknowledge provision of SAXS beamtime at BM29 at ESRF (Grenoble, France) and thank Dr. Mark Tully and the PSCM lab for support during the SAXS experiment. We also acknowledge the Norwegian national infrastructure for X-ray diffraction and scattering (RECX) at the University of Oslo (Norway) for SAXS beamtime, as well as SANS beamtime at KWS-2 at MLZ (Garching, Germany) and Sans2d(101-102103) at ISIS (Didcot, United Kingdom) where we received additional help from Dr. Leide Cavalcanti. Furthermore, we acknowledge support from a supercomputing grant from Northwestern University High Performance Computing Center.

Keywords

Peptide-assembly
computer simulation
molecular exchange
nanostructured peptides
peptide−polymer conjugates
small-angle scattering
structural stability

ASJC Scopus subject areas

General Materials Science
General Engineering
General Physics and Astronomy

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10.1021/acsnano.3c01811

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abstract = "Often nanostructures formed by self-assembly of small molecules based on hydrophobic interactions are rather unstable, causing morphological changes or even dissolution when exposed to changes in aqueous media. In contrast, peptides offer precise control of the nanostructure through a range of molecular interactions where physical stability can be engineered in and, to a certain extent, decoupled from size via rational design. Here, we investigate a family of peptides that form beta-sheet nanofibers and demonstrate a remarkable physical stability even after attachment of poly(ethylene glycol). We employed small-angle neutron/X-ray scattering, circular dichroism spectroscopy, and molecular dynamics simulation techniques to investigate the detailed nanostructure, stability, and molecular exchange. The results for the most stable sequence did not reveal any structural alterations or unimer exchange for temperatures up to 85 °C in the biologically relevant pH range. Only under severe mechanical perturbation (i.e., tip sonication) would the fibers break up, which is reflected in a very high activation barrier for unimer exchange of ∼320 kJ/mol extracted from simulations. The results give important insight into the relation between molecular structure and stability of peptide nanostructure that is important for, e.g., biomedical applications.",

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AU - König, Nico

AU - Szostak, Szymon Mikolaj

AU - Nielsen, Josefine Eilsø

AU - Dunbar, Martha

AU - Yang, Su

AU - Chen, Weike

AU - Benjamin, Ari

AU - Radulescu, Aurel

AU - Mahmoudi, Najet

AU - Willner, Lutz

AU - Keten, Sinan

AU - Dong, He

AU - Lund, Reidar

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Stability of Nanopeptides: Structure and Molecular Exchange of Self-assembled Peptide Fibers

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