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Targeting Cellular Lipid Rafts for Dynamic Nuclear Polarization Nuclear Magnetic Resonance.

Sarah A Overall1, Agnes Eck1, Ancy T Wilson2

  • 1Institute of Molecular Physical Sciences, ETH Zurich, Zurich, Switzerland.

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|February 28, 2026
PubMed
Summary
This summary is machine-generated.

Investigating lipid rafts, crucial cell platforms, is challenging. This study introduces in-cell dynamic nuclear polarization NMR to visualize these structures, identifying cross-effect efficiency as a key factor for future development.

Keywords:
hyperpolarizationin‐cell dynamic nuclear polarization‐nuclear magnetic resonancelipid raftsolid‐state nuclear magnetic reosnancetargeted dynamic nuclear poarization

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Biophysics

Background:

  • Lipid rafts are vital membrane microdomains for protein localization and signaling.
  • Understanding how non-myristylated molecules target and stabilize within lipid rafts is limited.
  • Current techniques lack the angstrom resolution needed to study these membrane microdomains.

Purpose of the Study:

  • To develop and validate a novel method for investigating lipid rafts using in-cell dynamic nuclear polarization (DNP) NMR.
  • To explore the structural interactions governing molecule localization and stabilization within lipid rafts.
  • To identify limitations and future directions for targeted DNP of cellular structures.

Main Methods:

  • Covalent linkage of the polarizing agent AsymPol to the raft-specific protein Ostreolysin A (OlyA).
  • Application of in-cell dynamic nuclear polarization (DNP) NMR spectroscopy.
  • Validation of method specificity using fluorescence microscopy.
  • Analysis of DNP buildup curves to assess OlyA localization.

Main Results:

  • Demonstrated specificity of the DNP-NMR approach for lipid raft investigation.
  • Achieved DNP enhancements at low concentrations of spin-labeled OlyA.
  • Identified heterogeneous localization of OlyA within lipid rafts.
  • Pinpointed cross-effect efficiency as a critical limiting factor for targeted DNP.

Conclusions:

  • In-cell DNP NMR offers a promising avenue for studying lipid rafts at high resolution.
  • Cross-effect efficiency must be optimized for effective targeted DNP of membrane microdomains.
  • This work provides a foundation for advancing techniques to probe lipid raft structure and function.