title: Cationic nanoparticles induce nanoscale disruption in living cell plasma membranes.
abstract: It has long been recognized that cationic nanoparticles induce cell membrane permeability. Recently, it has been found that cationic nanoparticles induce the formation and/or growth of nanoscale holes in supported lipid bilayers. In this paper, we show that noncytotoxic concentrations of cationic nanoparticles induce 30-2000 pA currents in 293A (human embryonic kidney) and KB (human epidermoid carcinoma) cells, consistent with a nanoscale defect such as a single hole or group of holes in the cell membrane ranging from 1 to 350 nm(2) in total area. Other forms of nanoscale defects, including the nanoparticle porating agents adsorbing onto or intercalating into the lipid bilayer, are also consistent; although the size of the defect must increase to account for any reduction in ion conduction, as compared to a water channel. An individual defect forming event takes 1-100 ms, while membrane resealing may occur over tens of seconds. Patch-clamp data provide direct evidence for the formation of nanoscale defects in living cell membranes. The cationic polymer data are compared and contrasted with patch-clamp data obtained for an amphiphilic phenylene ethynylene antimicrobial oligomer (AMO-3), a small molecule that is proposed to make well-defined 3.4 nm holes in lipid bilayers. Here, we observe data that are consistent with AMO-3 making approximately 3 nm holes in living cell membranes.
authors.affiliation: Chemistry Department, Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Jiumei
authors.initials: J
authors.lastname: Chen
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Hessler
authors.forename: Krishna
authors.initials: K
authors.lastname: Putchakayala
authors.forename: Brian K
authors.initials: BK
authors.lastname: Panama
authors.forename: Damian P
authors.initials: DP
authors.lastname: Khan
authors.forename: Seungpyo
authors.initials: S
authors.lastname: Hong
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Mullen
authors.forename: Stassi C
authors.initials: SC
authors.lastname: Dimaggio
authors.forename: Abhigyan
authors.initials: A
authors.lastname: Som
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Tew
authors.forename: Anatoli N
authors.initials: AN
authors.lastname: Lopatin
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
authors.forename: Mark M Banaszak
authors.initials: MM
authors.lastname: Holl
authors.forename: Bradford G
authors.initials: BG
authors.lastname: Orr
mesh_terms: D002412:Cations; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D053758:Nanoparticles; D036103:Nanotechnology
chemical_list: D002412:Cations