1. Cell Biology

Magnetic resonance measurements of cellular and sub-cellular membrane structures in live and fixed neural tissue

  1. Nathan H Williamson
  2. Rea Ravin
  3. Dan Benjamini
  4. Hellmut Merkle
  5. Melanie Falgairolle
  6. Michael James O'Donovan
  7. Dvir Blivis
  8. Dave Ide
  9. Teddy X Cai
  10. Nima S Ghorashi
  11. Ruiliang Bai
  12. Peter J Basser  Is a corresponding author
  1. Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States
  2. National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States
  3. National Institute of Mental Health, National Institutes of Health, United States
  4. National Heart, Lung, and Blood Institute, National Institutes of Health, United States
  5. Zhejiang University, China
https://doi.org/10.7554/eLife.51101
Share this article
Cite this article
  1. Nathan H Williamson
  2. Rea Ravin
  3. Dan Benjamini
  4. Hellmut Merkle
  5. Melanie Falgairolle
  6. Michael James O'Donovan
  7. Dvir Blivis
  8. Dave Ide
  9. Teddy X Cai
  10. Nima S Ghorashi
  11. Ruiliang Bai
  12. Peter J Basser
(2019)
Magnetic resonance measurements of cellular and sub-cellular membrane structures in live and fixed neural tissue
eLife 8:e51101.
https://doi.org/10.7554/eLife.51101
  2. Download BibTeX
  3. Download .RIS

Abstract

We develop magnetic resonance (MR) methods for real-time measurement of tissue microstructure and membrane permeability of live and fixed excised neonatal mouse spinal cords. Diffusion and exchange MR measurements are performed using the strong static gradient produced by a single-sided permanent magnet. Using tissue delipidation methods, we show that water diffusion is restricted solely by lipid membranes. Most of the diffusion signal can be assigned to water in tissue which is far from membranes. The remaining 25% can be assigned to water restricted on length scales of roughly a micron or less, near or within membrane structures at the cellular, organelle, and vesicle levels. Diffusion exchange spectroscopy measures water exchanging between membrane structures and free environments at 100 s-1.

Data availability

Source data for all Figures 1-9 in the manuscript have been provided as supporting files.

Article and author information

Author details

  1. Nathan H Williamson

    Section on Quantitative Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0221-9121

  2. Rea Ravin

    Section on Quantitative Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Dan Benjamini

    Section on Quantitative Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Hellmut Merkle

    National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Melanie Falgairolle

    National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5243-4714

  6. Michael James O'Donovan

    National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2487-7547

  7. Dvir Blivis

    National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6203-7325

  8. Dave Ide

    National Institute of Mental Health, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Teddy X Cai

    Section on Quantitative Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. Nima S Ghorashi

    Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.

  11. Ruiliang Bai

    Interdisciplinary Institute of Neuroscience and Technology, Qiushi Academy for Advanced Studies; College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.

  12. Peter J Basser

    Section on Quantitative Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    For correspondence
    pjbasser@helix.nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4795-6088

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (Intramural Research Program (IRP))

  • Nathan H Williamson
  • Rea Ravin
  • Dan Benjamini
  • Teddy X Cai
  • Ruiliang Bai
  • Peter J Basser

National Institute of Neurological Disorders and Stroke (IRP)

  • Hellmut Merkle
  • Melanie Falgairolle
  • Michael James O'Donovan
  • Dvir Blivis
  • Dave Ide

National Institute of Mental Health (IRP)

  • Dave Ide

National Heart, Lung, and Blood Institute (IRP)

  • Nima S Ghorashi

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments were carried out in compliance with the National Institute of Neurological Disorders and Stroke Animal Care and Use Committee (Animal Protocol Number 1267-18).

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 1,689
    views
  • 240
    downloads
  • 52
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Nathan H Williamson
  2. Rea Ravin
  3. Dan Benjamini
  4. Hellmut Merkle
  5. Melanie Falgairolle
  6. Michael James O'Donovan
  7. Dvir Blivis
  8. Dave Ide
  9. Teddy X Cai
  10. Nima S Ghorashi
  11. Ruiliang Bai
  12. Peter J Basser
(2019)
Magnetic resonance measurements of cellular and sub-cellular membrane structures in live and fixed neural tissue
eLife 8:e51101.
https://doi.org/10.7554/eLife.51101

Share this article

https://doi.org/10.7554/eLife.51101

Categories and tags

Research organism

Further reading

    1. Cell Biology

    Small-molecule activation of TFEB alleviates Niemann–Pick disease type C via promoting lysosomal exocytosis and biogenesis

    Kaili Du, Hongyu Chen ... Dan Li
    Research Article

    Niemann–Pick disease type C (NPC) is a devastating lysosomal storage disease characterized by abnormal cholesterol accumulation in lysosomes. Currently, there is no treatment for NPC. Transcription factor EB (TFEB), a member of the microphthalmia transcription factors (MiTF), has emerged as a master regulator of lysosomal function and promoted the clearance of substrates stored in cells. However, it is not known whether TFEB plays a role in cholesterol clearance in NPC disease. Here, we show that transgenic overexpression of TFEB, but not TFE3 (another member of MiTF family) facilitates cholesterol clearance in various NPC1 cell models. Pharmacological activation of TFEB by sulforaphane (SFN), a previously identified natural small-molecule TFEB agonist by us, can dramatically ameliorate cholesterol accumulation in human and mouse NPC1 cell models. In NPC1 cells, SFN induces TFEB nuclear translocation via a ROS-Ca2+-calcineurin-dependent but MTOR-independent pathway and upregulates the expression of TFEB-downstream genes, promoting lysosomal exocytosis and biogenesis. While genetic inhibition of TFEB abolishes the cholesterol clearance and exocytosis effect by SFN. In the NPC1 mouse model, SFN dephosphorylates/activates TFEB in the brain and exhibits potent efficacy of rescuing the loss of Purkinje cells and body weight. Hence, pharmacological upregulating lysosome machinery via targeting TFEB represents a promising approach to treat NPC and related lysosomal storage diseases, and provides the possibility of TFEB agonists, that is, SFN as potential NPC therapeutic candidates.

    1. Cell Biology

    Stratification of enterochromaffin cells by single-cell expression analysis

    Yan Song, Linda J Fothergill ... Gene W Yeo
    Research Article

    Dynamic interactions between gut mucosal cells and the external environment are essential to maintain gut homeostasis. Enterochromaffin (EC) cells transduce both chemical and mechanical signals and produce 5-hydroxytryptamine to mediate disparate physiological responses. However, the molecular and cellular basis for functional diversity of ECs remains to be adequately defined. Here, we integrated single-cell transcriptomics with spatial image analysis to identify 14 EC clusters that are topographically organized along the gut. Subtypes predicted to be sensitive to the chemical environment and mechanical forces were identified that express distinct transcription factors and hormones. A Piezo2+ population in the distal colon was endowed with a distinctive neuronal signature. Using a combination of genetic, chemogenetic, and pharmacological approaches, we demonstrated Piezo2+ ECs are required for normal colon motility. Our study constructs a molecular map for ECs and offers a framework for deconvoluting EC cells with pleiotropic functions.

    1. Cell Biology
    2. Developmental Biology

    Lens Development: Bringing signaling complexity into focus

    Sarah Y Coomson, Salil A Lachke
    Insight

    A study in mice reveals key interactions between proteins involved in fibroblast growth factor signaling and how they contribute to distinct stages of eye lens development.