title: Vacuolization in Cytoplasm and Cell Membrane Permeability Enhancement Triggered by Micrometer-Sized Graphene Oxide.
abstract: A deep understanding of the interaction of a graphene oxide (GO) sheet with cells at the molecular level may expedite its biomedical application and predict its new functions and adverse effects. Herein we inspect the interaction between micrometer-sized GO (mGO), commonly used in biomedical research, and cells at the molecular level through a variety of techniques. A major finding is that, instead of direct cellular penetration, the mGO sheets can stimulate the cellular response by interacting with the membrane protein and the membrane. Specifically, it is illustrated that even within a short exposure time the mGO sheets can induce the formation of vacuoles in the cytosolic compartment and enhance the cell permeability. The vacuolization is only observed in the cells that strongly express aquaporin (AQP1), indicating the specific interaction of the mGO with AQP1. Moreover, inhibition of the AQP1 activity prevents the formation of vacuoles, revealing that the interaction of the mGO with AQP1 occurs most probably at the vestibule of AQP1 at the extracellular side. Additionally, though the cell permeability was enhanced, it only improves the penetration of small molecules, not for macromolecules such as proteins. These findings are potentially valuable in cancer therapy because AQPs are strongly expressed in tumor cells of different origins, particularly aggressive tumors, and it will also be beneficial for drug transport across barrier membranes.
authors.affiliation: Department of Electronic Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University , Shanghai 200240, P.R. China.
authors.forename: Congyu
authors.initials: C
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology , Shanghai, 200237. P.R. China.
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology , Shanghai, 200237. P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology , Shanghai, 200237. P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology , Shanghai, 200237. P.R. China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Electronic Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University , Shanghai 200240, P.R. China.
authors.forename: Shouwu
authors.initials: S
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology , Shanghai, 200237. P.R. China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000588:Amines; D051398:Aquaporin 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D001692:Biological Transport; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects*; D005456:Fluorescent Dyes; D015870:Gene Expression; D017930:Genes, Reporter; D006108:Graphite / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008627:Mercuric Chloride / Q000494:pharmacology; D046529:Microscopy, Electron, Transmission; D010087:Oxides; D014617:Vacuoles / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D014867:Water / Q000378:metabolism
chemical_list: C496020:AQP1 protein, human; D000588:Amines; D005456:Fluorescent Dyes; D010087:Oxides; C493330:Red DND-99; D014867:Water; D051398:Aquaporin 1; D049452:Green Fluorescent Proteins; D008627:Mercuric Chloride; D006108:Graphite
keywords: AQPs; aquaporins; cell membrane; mGO; micrometer-sized graphene oxide