Differential modulation of endothelial cytoplasmic protrusions after exposure to graphene-family nanomaterials.
2-D nanomaterials
Cell-material interactions
Cytoplasmic protrusions
Endothelial cells
Nanosafety
Journal
NanoImpact
ISSN: 2452-0748
Titre abrégé: NanoImpact
Pays: Netherlands
ID NLM: 101676795
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
17
12
2021
revised:
12
04
2022
accepted:
14
04
2022
pubmed:
14
5
2022
medline:
7
6
2022
entrez:
13
5
2022
Statut:
ppublish
Résumé
Engineered nanomaterials offer the benefit of having systematically tunable physicochemical characteristics (e.g., size, dimensionality, and surface chemistry) that highly dictate the biological activity of a material. Among the most promising engineered nanomaterials to date are graphene-family nanomaterials (GFNs), which are 2-D nanomaterials (2DNMs) with unique electrical and mechanical properties. Beyond engineering new nanomaterial properties, employing safety-by-design through considering the consequences of cell-material interactions is essential for exploring their applicability in the biomedical realm. In this study, we asked the effect of GFNs on the endothelial barrier function and cellular architecture of vascular endothelial cells. Using micropatterned cell pairs as a reductionist in vitro model of the endothelium, the progression of cytoskeletal reorganization as a function of GFN surface chemistry and time was quantitatively monitored. Here, we show that the surface oxidation of GFNs (graphene, reduced graphene oxide, partially reduced graphene oxide, and graphene oxide) differentially affect the endothelial barrier at multiple scales; from the biochemical pathways that influence the development of cellular protrusions to endothelial barrier integrity. More oxidized GFNs induce higher endothelial permeability and the increased formation of cytoplasmic protrusions such as filopodia. We found that these changes in cytoskeletal organization, along with barrier function, can be potentiated by the effect of GFNs on the Rho/Rho-associated kinase (ROCK) pathway. Specifically, GFNs with higher surface oxidation elicit stronger ROCK2 inhibitory behavior as compared to pristine graphene sheets. Overall, findings from these studies offer a new perspective towards systematically controlling the surface-dependent effects of GFNs on cytoskeletal organization via ROCK2 inhibition, providing insight for implementing safety-by-design principles in GFN manufacturing towards their targeted biomedical applications.
Identifiants
pubmed: 35560286
pii: S2452-0748(22)00023-4
doi: 10.1016/j.impact.2022.100401
pmc: PMC9812361
mid: NIHMS1858252
pii:
doi:
Substances chimiques
Graphite
7782-42-5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
100401Subventions
Organisme : NHLBI NIH HHS
ID : T32 HL007572
Pays : United States
Organisme : NIEHS NIH HHS
ID : U01 ES027272
Pays : United States
Organisme : NIEHS NIH HHS
ID : U24 ES026946
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier B.V. All rights reserved.
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