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Speeding up Biomimetic Nuclear Magnetic Resonance

Speeding up Biomimetic Nuclear Magnetic Resonance

Dennis Kurzbach (ORCID: 0000-0001-6455-2136)
  • Grant DOI 10.55776/P33338
  • Funding program Principal Investigator Projects
  • Status ended
  • Start October 1, 2020
  • End December 31, 2024
  • Funding amount € 383,439
  • Project website

Disciplines

Biology (15%); Chemistry (85%)

Keywords

    Nuclear Magnetic Resonance, Biomineralization, Real-Time NMR, Biomimicry, Hyperpolarization

Abstract Final report

The crystallization of minerals is an important natural process involved, for example, in the formation of bone, teeth or carapace. However, our understanding of the underlying processes at the atomic and molecular level is still incomplete. This remains to be the case even if it would be quite useful to gain deeper insights into these processes in order to, e.g. optimize bone prosthetics or to develop new functional materials. The project "Biomimetic nuclear magnetic resonance" aims to deepen this understanding of mineralization by developing methods that allow one to follow such processes in a time-resolved manner at the molecular level. NMR (nuclear magnetic resonance) is one of the most important methods for determining the structures of molecules in solution, albeit limited time resolution. In order to enable real-time monitoring of processes based on NMR spectroscopy, the project aims to develop a new method based on hyperpolarization techniques (more precisely through dissolution dynamic nuclear polarization, short D-DNP) that can provide 10.000-fold signal amplifications for NMR measurements. This enables tracking of molecular processes in a time-resolved manner. The principle is: The stronger a signal, the shorter it has to be observed for a measurement. Thus, if the time per NMR measurement can be reduced, it will be possible to quickly and successively detect series of spectra, which in turn enables time resolution." With this, D-DNP enables monitoring of fast processes - even in the millisecond range while simultaneously distinguishing individual atoms. A special focus of the project lies on understanding biomineralization processes and their initial stages. Biomineralization denotes the ability of living organisms to produce solid materials. For such process, for example in bone formation events, precursors of crystallization nuclei emerge within milliseconds when calcium and phosphate ions meet in solution. These species, which appear at the beginning of the crystallization process, are to be characterized analytically in the project and observed with high- resolution methods in order to comprehensively describe biominerals and their underlying chemical processes with new insights and technologies. The project aims, e.g. at clarifying whether the size of the newly discovered precursor species can be controlled and whether it can influence the hardness or brittleness of the macroscopic material that will be emerge through the mineralization process. In addition, a contribution is envisaged to a long-standing dispute about the theory behind biomineralization, i.e. to clarify whether the crystallization seed precursors fir in the classic theoretical framework of mineralization that has been developed over decades or if new non-classical theories need to be devised.

The crystallization of minerals is an important natural process, for example in the formation of bones, teeth, or animal shells. However, our understanding of the underlying processes at the atomic and molecular level remains incomplete. This is despite the fact that gaining deeper insights into these processes would be beneficial-for instance, to optimize bone prostheses or to develop new functional materials. The project "Biomimetic Nuclear Magnetic Resonance" aims to deepen our understanding of mineralization by developing methods that allow such processes to be tracked in real time at the molecular level. NMR (nuclear magnetic resonance) is one of the most important techniques for determining the structure of molecules in solution, though it has limited time resolution. To enable real-time observation of processes based on NMR spectroscopy, the project aims to develop a new method using so-called hyperpolarization-specifically, dissolution dynamic nuclear polarization (D-DNP)-which allows up to a 10,000-fold signal enhancement in NMR measurements. This enhancement makes it possible to monitor molecular processes with time resolution. The underlying principle is: "The stronger a signal, the shorter the time needed to observe it in a measurement. So if the time per NMR measurement can be reduced, rapid measurement series become possible, which in turn enables time resolution." D-DNP thus makes it possible to follow fast processes-even those occurring in the millisecond range-while distinguishing individual atoms. A special focus of the project is to understand biomineralization processes and their initial stages. Biomineralization is the ability of living organisms to produce solid materials. In such processes-for example, during bone formation-precursors of crystallization nuclei form within milliseconds, for instance when calcium and phosphate ions come into contact in solution. These species, which occur at the onset of the crystallization process, are to be analytically characterized and observed using high-resolution methods, in order to describe biominerals and the underlying chemical processes more comprehensively with new insights and technology. One aim, for example, is to determine whether the size of these newly discovered precursor species can be controlled, and whether this in turn can influence the hardness or brittleness of the resulting macroscopic material. In addition, the project seeks to contribute to a longstanding debate over the theory of biomineralization-specifically, whether these precursors to crystallization nuclei fit within the classical theoretical framework of mineralization developed over decades, or whether new, non-classical theories need to be formulated.

Research institution(s)
  • Universität Wien - 100%
International project participants
  • Thierry Azais, Sorbonne Université - France

Research Output

  • 133 Citations
  • 23 Publications
  • 1 Policies
  • 1 Methods & Materials
  • 10 Datasets & models
  • 4 Disseminations
  • 1 Scientific Awards
  • 1 Fundings
Publications
  • 2025
    Title The Internal Structural Dynamics of Elastin-Like Polypeptide Assemblies by 13 C-Direct Detected NMR Spectroscopy
    DOI 10.1021/acs.analchem.4c05163
    Type Journal Article
    Author Brandis D
    Journal Analytical Chemistry
  • 2024
    Title Hyperpolarized nuclear Overhauser enhancement of alanine methyl groups by doubly relayed proton exchange.
    DOI 10.1016/j.jmr.2024.107727
    Type Journal Article
    Author Turhan E
    Journal Journal of magnetic resonance (San Diego, Calif. : 1997)
    Pages 107727
  • 2024
    Title An Atomistic View on the Mechanism of Diatom Peptide-Guided Biomimetic Silica Formation.
    DOI 10.1002/advs.202401239
    Type Journal Article
    Author Brandis D
    Journal Advanced science (Weinheim, Baden-Wurttemberg, Germany)
  • 2024
    Title Branched Polymeric Prenucleation Assemblies Initiate Calcium Phosphate Precipitation.
    DOI 10.1021/jacs.4c07325
    Type Journal Article
    Author Goldberga I
    Journal Journal of the American Chemical Society
    Pages 25614-25624
  • 2024
    Title Implementation of a rapid injection system to enable reproducible real-time monitoring of nonclassical crystallization pathways by parallel detected hyperpolarization
    Type PhD Thesis
    Author Ertan Turhan
  • 2024
    Title Multimodal Characterization of in vitro Biogenic Silicification by Silaffin (based) Peptides
    Type PhD Thesis
    Author Fanny Kozak
  • 2024
    Title Short-lived calcium carbonate precursors observed in situ via Bullet-dynamic nuclear polarization.
    DOI 10.1038/s42004-024-01300-5
    Type Journal Article
    Author Minaei M
    Journal Communications chemistry
    Pages 210
  • 2022
    Title Hyperpolarized water as universal sensitivity booster in biomolecular NMR
    DOI 10.1038/s41596-022-00693-8
    Type Journal Article
    Author Hilty C
    Journal Nature Protocols
    Pages 1621-1657
  • 2022
    Title Inversion of Hyperpolarized 13C NMR Signals through Cross-Correlated Cross-Relaxation in Dissolution DNP Experiments
    DOI 10.1021/acs.jpcb.2c03375
    Type Journal Article
    Author Negroni M
    Journal The Journal of Physical Chemistry B
    Pages 4599-4610
    Link Publication
  • 2023
    Title Understanding Self-Assembly of Silica-Precipitating Peptides to Control Silica Particle Morphology.
    DOI 10.1002/adma.202207586
    Type Journal Article
    Author Kozak F
    Journal Advanced materials (Deerfield Beach, Fla.)
  • 2022
    Title Nuclear Overhauser spectroscopy in hyperpolarized water – chemical vs. magnetic exchange
    DOI 10.1039/d2cc03735a
    Type Journal Article
    Author Epasto L
    Journal Chemical Communications
    Pages 11661-11664
    Link Publication
  • 2022
    Title Toward protein NMR at physiological concentrations by hyperpolarized water—Finding and mapping uncharted conformational spaces
    DOI 10.1126/sciadv.abq5179
    Type Journal Article
    Author Epasto L
    Journal Science Advances
    Link Publication
  • 2023
    Title Biphasic NMR of Hyperpolarized Suspensions-Real-Time Monitoring of Solute-to-Solid Conversion to Watch Materials Grow.
    DOI 10.1021/acs.jpcc.3c04198
    Type Journal Article
    Author Pötzl C
    Journal The journal of physical chemistry. C, Nanomaterials and interfaces
    Pages 19591-19598
  • 2022
    Title Frémy’s Salt as a Low-Persistence Hyperpolarization Agent: Efficient Dynamic Nuclear Polarization Plus Rapid Radical Scavenging
    DOI 10.1021/jacs.2c07960
    Type Journal Article
    Author Negroni M
    Journal Journal of the American Chemical Society
    Pages 20680-20686
    Link Publication
  • 2021
    Title A novel sample handling system for dissolution dynamic nuclear polarization experiments
    DOI 10.5194/mr-2021-12
    Type Preprint
    Author Kress T
    Pages 1-8
    Link Publication
  • 2021
    Title A novel sample handling system for dissolution dynamic nuclear polarization experiments
    DOI 10.5194/mr-2-387-2021
    Type Journal Article
    Author Kress T
    Journal Magnetic Resonance
    Pages 387-394
    Link Publication
  • 2021
    Title How to assess the structural dynamics of transcription factors by integrating sparse NMR and EPR constraints with molecular dynamics simulations
    DOI 10.1016/j.csbj.2021.04.020
    Type Journal Article
    Author Kozak F
    Journal Computational and Structural Biotechnology Journal
    Pages 2097-2105
    Link Publication
  • 2021
    Title Residue-resolved monitoring of protein hyperpolarization at sub-second time resolution
    DOI 10.21203/rs.3.rs-830313/v1
    Type Preprint
    Author Kurzbach D
  • 2021
    Title Formation and Evolution of Nanoscale Calcium Phosphate Precursors under Biomimetic Conditions
    DOI 10.1021/acs.analchem.1c01561
    Type Journal Article
    Author Epasto L
    Journal Analytical Chemistry
    Pages 10204-10211
    Link Publication
  • 2021
    Title Residue-resolved monitoring of protein hyperpolarization at sub-second time resolution
    DOI 10.1038/s42004-021-00587-y
    Type Journal Article
    Author Negroni M
    Journal Communications Chemistry
    Pages 147
    Link Publication
  • 2021
    Title Evaporation-Induced Self-Assembly of Small Peptide-Conjugated Silica Nanoparticles
    DOI 10.1002/anie.202108378
    Type Journal Article
    Author Von Baeckmann C
    Journal Angewandte Chemie International Edition
    Pages 22700-22705
    Link Publication
  • 2021
    Title Evaporation-Induced Self-Assembly of Small Peptide-Conjugated Silica Nanoparticles
    DOI 10.1002/ange.202108378
    Type Journal Article
    Author Von Baeckmann C
    Journal Angewandte Chemie
    Pages 22882-22887
    Link Publication
  • 2021
    Title Conformational selection of vasopressin upon V1a receptor binding
    DOI 10.1016/j.csbj.2021.10.024
    Type Journal Article
    Author Che K
    Journal Computational and Structural Biotechnology Journal
    Pages 5826-5833
    Link Publication
Policies
  • 2021
    Title PhD Training
    Type Influenced training of practitioners or researchers
Methods & Materials
  • 2023
    Title Hyperpolraized NMR
    Type Technology assay or reagent
    Public Access
Datasets & models
  • 2025 Link
    Title Data Set for The Internal Structural Dynamics of Elastin-Like Polypeptide Assemblies by 13C-Direct Detected NMR Spectroscopy
    Type Database/Collection of data
    Public Access
    Link Link
  • 2024 Link
    Title Data Set for Bullet-DNP enables in-situ observation of multiple short-lived calcium carbonate precursors
    Type Database/Collection of data
    Public Access
    Link Link
  • 2024 Link
    Title Data Set for Branched Polymeric Prenucleation Assemblies Initiate Calcium Phosphate Precipitation
    Type Database/Collection of data
    Public Access
    Link Link
  • 2023 Link
    Title Data Set for Turhan et al - Biphasic NMR of hyperpolarized suspensions
    DOI 10.5281/zenodo.8325082
    Type Database/Collection of data
    Public Access
    Link Link
  • 2022 Link
    Title Data Set for Negroni et al. Inversion of Hyperpolarized 13C NMR Signals Through Cross-Correlated Cross-Relaxation in Disso-lution DNP Experiments
    DOI 10.5281/zenodo.6580927
    Type Database/Collection of data
    Public Access
    Link Link
  • 2022 Link
    Title Data Set for Negroni et al. - Frémy's Salt as a Low-Persistence Hyperpolarization Agent: Efficient Dynamic Nuclear Polarization Plus Rapid Radical Scavenging
    DOI 10.5281/zenodo.7261375
    Type Database/Collection of data
    Public Access
    Link Link
  • 2022 Link
    Title Data Set for Epasto et al. - Towards Protein NMR at Physiological Concentrations by Hyperpolarized Water
    DOI 10.5281/zenodo.6701088
    Type Database/Collection of data
    Public Access
    Link Link
  • 2021 Link
    Title Data Set for Epasto et al. - Formation and Evolution of Nanoscale Calcium Phosphate Precursors under Biomimetic Conditions
    DOI 10.5281/zenodo.5511748
    Type Database/Collection of data
    Public Access
    Link Link
  • 2021 Link
    Title Data Set for Kress et al. - A novel sample handling system for dissolution dynamic nuclear polarization experiments
    DOI 10.5281/zenodo.4738932
    Type Database/Collection of data
    Public Access
    Link Link
  • 2021 Link
    Title Data Set for Negroni et al. - Residue-resolved monitoring of protein hyperpolarization at sub-second time resolution
    DOI 10.5281/zenodo.5547223
    Type Database/Collection of data
    Public Access
    Link Link
Disseminations
  • 2022
    Title Lange Nacht der Wissenschaft
    Type A talk or presentation
  • 2022
    Title Press Release - Magnetic Resonance Makes the Invisible Visible
    Type A press release, press conference or response to a media enquiry/interview
  • 2022
    Title Press Release - Pimp my Spec: Upgrade for Magnetic Resonance Methods with a 1,000-fold Amplifier
    Type A press release, press conference or response to a media enquiry/interview
  • 2020
    Title Press Release - Die Natur enthüllt sich der Wissenschaft
    Type A press release, press conference or response to a media enquiry/interview
Scientific Awards
  • 2022
    Title Ignaz L. Lieben Award
    Type Research prize
    Level of Recognition Continental/International
Fundings
  • 2020
    Title Speeding up Biomimetic Nuclear Magnetic Resonance
    Type Research grant (including intramural programme)
    Start of Funding 2020
    Funder Austrian Science Fund (FWF)

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