A cell-based computational modeling approach for developing site-directed molecular probes.

Modeling the local absorption and retention patterns of membrane-permeant small molecules in a cellular context could facilitate development of site-directed chemical agents for bioimaging or therapeutic applications. Here, we present an integrative approach to this problem, combining in silico comp...

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Autores principales:	Jing-Yu Yu, Nan Zheng, Gerta Mane, Kyoung Ah Min, Juan P Hinestroza, Huaning Zhu, Kathleen A Stringer, Gus R Rosania
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/479eaf9397424fa08218a3a44784a9e1
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spelling	oai:doaj.org-article:479eaf9397424fa08218a3a44784a9e12021-11-18T05:51:34ZA cell-based computational modeling approach for developing site-directed molecular probes.1553-734X1553-735810.1371/journal.pcbi.1002378https://doaj.org/article/479eaf9397424fa08218a3a44784a9e12012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22383866/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Modeling the local absorption and retention patterns of membrane-permeant small molecules in a cellular context could facilitate development of site-directed chemical agents for bioimaging or therapeutic applications. Here, we present an integrative approach to this problem, combining in silico computational models, in vitro cell based assays and in vivo biodistribution studies. To target small molecule probes to the epithelial cells of the upper airways, a multiscale computational model of the lung was first used as a screening tool, in silico. Following virtual screening, cell monolayers differentiated on microfabricated pore arrays and multilayer cultures of primary human bronchial epithelial cells differentiated in an air-liquid interface were used to test the local absorption and intracellular retention patterns of selected probes, in vitro. Lastly, experiments involving visualization of bioimaging probe distribution in the lungs after local and systemic administration were used to test the relevance of computational models and cell-based assays, in vivo. The results of in vivo experiments were consistent with the results of in silico simulations, indicating that mitochondrial accumulation of membrane permeant, hydrophilic cations can be used to maximize local exposure and retention, specifically in the upper airways after intratracheal administration.Jing-Yu YuNan ZhengGerta ManeKyoung Ah MinJuan P HinestrozaHuaning ZhuKathleen A StringerGus R RosaniaPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 2, p e1002378 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Jing-Yu Yu Nan Zheng Gerta Mane Kyoung Ah Min Juan P Hinestroza Huaning Zhu Kathleen A Stringer Gus R Rosania A cell-based computational modeling approach for developing site-directed molecular probes.
description	Modeling the local absorption and retention patterns of membrane-permeant small molecules in a cellular context could facilitate development of site-directed chemical agents for bioimaging or therapeutic applications. Here, we present an integrative approach to this problem, combining in silico computational models, in vitro cell based assays and in vivo biodistribution studies. To target small molecule probes to the epithelial cells of the upper airways, a multiscale computational model of the lung was first used as a screening tool, in silico. Following virtual screening, cell monolayers differentiated on microfabricated pore arrays and multilayer cultures of primary human bronchial epithelial cells differentiated in an air-liquid interface were used to test the local absorption and intracellular retention patterns of selected probes, in vitro. Lastly, experiments involving visualization of bioimaging probe distribution in the lungs after local and systemic administration were used to test the relevance of computational models and cell-based assays, in vivo. The results of in vivo experiments were consistent with the results of in silico simulations, indicating that mitochondrial accumulation of membrane permeant, hydrophilic cations can be used to maximize local exposure and retention, specifically in the upper airways after intratracheal administration.
format	article
author	Jing-Yu Yu Nan Zheng Gerta Mane Kyoung Ah Min Juan P Hinestroza Huaning Zhu Kathleen A Stringer Gus R Rosania
author_facet	Jing-Yu Yu Nan Zheng Gerta Mane Kyoung Ah Min Juan P Hinestroza Huaning Zhu Kathleen A Stringer Gus R Rosania
author_sort	Jing-Yu Yu
title	A cell-based computational modeling approach for developing site-directed molecular probes.
title_short	A cell-based computational modeling approach for developing site-directed molecular probes.
title_full	A cell-based computational modeling approach for developing site-directed molecular probes.
title_fullStr	A cell-based computational modeling approach for developing site-directed molecular probes.
title_full_unstemmed	A cell-based computational modeling approach for developing site-directed molecular probes.
title_sort	cell-based computational modeling approach for developing site-directed molecular probes.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/479eaf9397424fa08218a3a44784a9e1
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A cell-based computational modeling approach for developing site-directed molecular probes.

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