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Title: A Framework of Paracellular Transport via Nanoparticles-Induced Endothelial Leakiness
Authors: Lee, Myeongsang
Ni, Nengyi
Tang, Huayuan
Li, Yuhuan
Wei, Wei
Kakinen, Aleksandr
Wan, Xulin
Davis, Thomas P.
Song, Yang
Leong, David Tai 
Ding, Feng
Ke, Pu Chun
Keywords: discrete molecular dynamics simulation
endothelial leakiness
signaling pathway
VE cadherin
Issue Date: 8-Sep-2021
Publisher: John Wiley and Sons Inc
Citation: Lee, Myeongsang, Ni, Nengyi, Tang, Huayuan, Li, Yuhuan, Wei, Wei, Kakinen, Aleksandr, Wan, Xulin, Davis, Thomas P., Song, Yang, Leong, David Tai, Ding, Feng, Ke, Pu Chun (2021-09-08). A Framework of Paracellular Transport via Nanoparticles-Induced Endothelial Leakiness. Advanced Science 8 (21) : 2102519. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Nanomaterial-induced endothelial leakiness (NanoEL) is an interfacial phenomenon denoting the paracellular transport of nanoparticles that is pertinent to nanotoxicology, nanomedicine and biomedical engineering. While the NanoEL phenomenon is complementary to the enhanced permeability and retention effect in terms of their common applicability to delineating the permeability and behavior of nanoparticles in tumoral environments, these two effects significantly differ in scope, origin, and manifestation. In the current study, the descriptors are fully examined of the NanoEL phenomenon elicited by generic citrate-coated gold nanoparticles (AuNPs) of changing size and concentration, from microscopic gap formation and actin reorganization down to molecular signaling pathways and nanoscale interactions of AuNPs with VE-cadherin and its intra/extracellular cofactors. Employing synergistic in silico methodologies, for the first time the molecular and statistical mechanics of cadherin pair disruption, especially in response to AuNPs of the smallest size and highest concentration are revealed. This study marks a major advancement toward establishing a comprehensive NanoEL framework for complementing the understanding of the transcytotic pathway and for guiding the design and application of future nanomedicines harnessing the myriad functions of the mammalian vasculature. © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH
Source Title: Advanced Science
ISSN: 2198-3844
DOI: 10.1002/advs.202102519
Rights: Attribution 4.0 International
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