title: Graphene-Induced Pore Formation on Cell Membranes.
abstract: Examining interactions between nanomaterials and cell membranes can expose underlying mechanisms of nanomaterial cytotoxicity and guide the design of safer nanomedical technologies. Recently, graphene has been shown to exhibit potential toxicity to cells; however, the molecular processes driving its lethal properties have yet to be fully characterized. We here demonstrate that graphene nanosheets (both pristine and oxidized) can produce holes (pores) in the membranes of A549 and Raw264.7 cells, substantially reducing cell viability. Electron micrographs offer clear evidence of pores created on cell membranes. Our molecular dynamics simulations reveal that multiple graphene nanosheets can cooperate to extract large numbers of phospholipids from the membrane bilayer. Strong dispersion interactions between graphene and lipid-tail carbons result in greatly depleted lipid density within confined regions of the membrane, ultimately leading to the formation of water-permeable pores. This cooperative lipid extraction mechanism for membrane perforation represents another distinct process that contributes to the molecular basis of graphene cytotoxicity.
authors.affiliation: Institute of Quantitative Biology and Medicine, SRMP and RAD-X, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.
authors.forename: Guangxin
authors.initials: G
authors.lastname: Duan
authors.affiliation: IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, USA.
authors.forename: Yuanzhao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, USA.
authors.forename: Binquan
authors.initials: B
authors.lastname: Luan
authors.affiliation: IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, USA.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Weber
authors.affiliation: Department of Oncology, The Affiliated Hospital of Nanjing Medical University, Changzhou No.2 People's Hospital, Changzhou, 213003, China.
authors.forename: Royce W
authors.initials: RW
authors.lastname: Zhou
authors.affiliation: Institute of Quantitative Biology and Medicine, SRMP and RAD-X, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.
authors.forename: Zaixing
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Institute of Quantitative Biology and Medicine, SRMP and RAD-X, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Institute of Quantitative Biology and Medicine, SRMP and RAD-X, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Xu
authors.affiliation: Institute of Quantitative Biology and Medicine, SRMP and RAD-X, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.|Department of Oncology, The Affiliated Hospital of Nanjing Medical University, Changzhou No.2 People's Hospital, Changzhou, 213003, China.
authors.forename: Judong
authors.initials: J
authors.lastname: Luo
authors.affiliation: Institute of Quantitative Biology and Medicine, SRMP and RAD-X, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.|IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, USA.|Department of Chemistry, Columbia University, New York, NY 10027, USA.
authors.forename: Ruhong
authors.initials: R
authors.lastname: Zhou
mesh_terms: D000072283:A549 Cells; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects* / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D006108:Graphite / Q000633:toxicity*; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D051379:Mice; D056004:Molecular Dynamics Simulation; D049329:Nanostructures / Q000633:toxicity; D010743:Phospholipids / Q000737:chemistry / Q000302:isolation & purification*; D000067996:RAW 264.7 Cells
chemical_list: D008051:Lipid Bilayers; D010743:Phospholipids; D006108:Graphite