TY - JOUR
T1 - Vacuolization in Cytoplasm and Cell Membrane Permeability Enhancement Triggered by Micrometer-Sized Graphene Oxide
AU - Wu, Congyu
AU - Wang, Chong
AU - Zheng, Jing
AU - Luo, Chao
AU - Li, Yanfang
AU - Guo, Shouwu
AU - Zhang, Jingyan
PY - 2015/8/25
Y1 - 2015/8/25
N2 - 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. (Figure Presented).
AB - 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. (Figure Presented).
KW - AQPs
KW - aquaporins
KW - cell membrane
KW - mGO
KW - micrometer-sized graphene oxide
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U2 - 10.1021/acsnano.5b01685
DO - 10.1021/acsnano.5b01685
M3 - Article
C2 - 26207693
AN - SCOPUS:84940061421
SN - 1936-0851
VL - 9
SP - 7913
EP - 7924
JO - ACS nano
JF - ACS nano
IS - 8
ER -