Molecular imaging with aquaporin-based reporter genes: quantitative considerations from Monte Carlo diffusion simulations.
Journal
bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187
Informations de publication
Date de publication:
11 Jun 2023
11 Jun 2023
Historique:
medline:
19
6
2023
pubmed:
19
6
2023
entrez:
19
6
2023
Statut:
epublish
Résumé
Aquaporins provide a new class of genetic tools for imaging molecular activity in deep tissues by increasing the rate of cellular water diffusion, which generates magnetic resonance contrast. However, distinguishing aquaporin contrast from the tissue background is challenging because water diffusion is also influenced by structural factors such as cell size and packing density. Here, we developed and experimentally validated a Monte Carlo model to analyze how cell radius and intracellular volume fraction quantitatively affect aquaporin signals. We demonstrated that a differential imaging approach based on time-dependent changes in diffusivity can improve specificity by unambiguously isolating aquaporin-driven contrast from the tissue background. Finally, we used Monte Carlo simulations to analyze the connection between diffusivity and the percentage of cells engineered to express aquaporin, and established a simple mapping that accurately determined the volume fraction of aquaporin-expressing cells in mixed populations. This study creates a framework for broad applications of aquaporins, particularly in biomedicine and in vivo synthetic biology, where quantitative methods to measure the location and performance of genetic devices in whole vertebrates are necessary.
Identifiants
pubmed: 37333205
doi: 10.1101/2023.06.09.544324
pmc: PMC10274877
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : NINDS NIH HHS
ID : R01 NS128278
Pays : United States
Organisme : NIDA NIH HHS
ID : R03 DA050971
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM133530
Pays : United States
Commentaires et corrections
Type : UpdateIn
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