Endothelial barrier dysfunction induced by nanoparticle exposure through actin remodeling via caveolae/raft-regulated calcium signalling

• Published in: NanoImpact Vol. 11; pp. 82 - 91
• Main Authors: Liu, Yizhong, Yoo, Eunsoo, Han, Chendong, Mahler, Gretchen J., Doiron, Amber L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2018
• Subjects: Gold; Permeability; Polystyrene; Silicon dioxide; Titanium dioxide; PS; DI; DLS; H2DCFDA; Silicon dioxide; FITC; FFT; HUVEC; CCK-8; Titanium dioxide; SiO2; PBS; Gold; MLCK; MLCP; GNPs; Permeability; Polystyrene; NPs; PEG; ROS; SEM; NTA; EGM-2; TiO2; gold; silicon dioxide; titanium dioxide; polystyrene; permeability
• ISSN: 2452-0748; 2452-0748
• DOI: 10.1016/j.impact.2018.02.007

The rapid development of modern nanotechnology has resulted in nanomaterial being use in nearly all applications of life, raising the potential risk of nanomaterial exposure alongside the need to design safe and effective materials. Previous work has demonstrated a specific effect of gold nanoparticles (GNPs) of approximately 20 nm on endothelial barrier function in vitro. To expand our understanding of this size-specific effect, titanium dioxide, silicon dioxide, and polystyrene nanoparticles (NPs) in this similar size range were studied. All tested nanoparticles were found to have minimal effects on cell viability, but exhibited a significant detrimental effect on endothelial barrier function. Nanoparticles in the size range of 20 to 30 nm were internalized by endothelial cells through caveolae/raft-mediated endocytosis, causing intracellular calcium elevation by approximately 30% at 2 h after administration, and triggering myosin light chain kinase (MLCK)-regulated actomyosin contraction. These effects culminated in an increase in endothelial monolayer permeability across all particle types within the 20–30 nm range. This nanoparticle exposure-induced endothelial barrier dysfunction may provide valuable information for designing safer nanomaterials or potential applications of this nanoparticle exposure-induced permeability effect in biomedicine. [Display omitted] •Nanoparticles in the 20 to 30 nm size range can cause endothelial barrier dysfunction without affecting cell proliferation.•Nanoparticles in the 20 to 30 nm size range are primarily internalized by caveolae/raft-regulated endocytosis.•Intracellular calcium level elevation induced by nanoparticle exposure triggers actin remodeling.