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Steady-state water exchange in neural tissue is primarily passive and through the phospholipid bilayer.

Created on 01 Aug 2026

Authors

Nathan H Williamson, Rea Ravin, Teddy X Cai, Julian A Rey, Peter J Basser

Published in

bioRxiv : the preprint server for biology. Jul 21, 2026. Epub Jul 21, 2026.

Abstract

Water molecules exchange incessantly across cell membranes and between intracellular compartments, but the dominant steady-state transport pathways, and whether they are active or passive, remain unclear. Low-field, high-gradient diffusion exchange spectroscopy (DEXSY) nuclear magnetic resonance (NMR) measurements on viable ex vivo neonatal mouse spinal cords show that water exchange is primarily passive. The apparent exchange rate constant (AXR) depends on osmotic conditions because it reflects multiple exchange pathways, each weighted by the exchanging compartments' volume fractions. A faster transmembrane path that becomes more visible with increasing extracellular space (ECS) fraction has a high activation energy but is ion-independent, suggesting passive transport through the phospholipid bilayer but not active or passive transport through co-transporter or channel proteins. A slower pathway which dominates when the extracelluar space shrinks has a low activation energy, consistent with geometric exchange between intracellular environments. Moreover, we show how DEXSY can be used to non-invasively measure tonicity in tissue, and inform us about the status of the tissue milieu. These findings may inform future translation to clinical MRI.
We use advanced nuclear magnetic resonance methods to address two unanswered questions in cellular biology: How does water exchange between tissue microenvironments under steady-state conditions, and do these processes involve active water cycling?

PMID:
42539266
Bibliographic data and abstract were imported from PubMed on 01 Aug 2026.

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