Wide Varieties of Cationic Nanoparticles Induce Defects in Supported Lipid Bilayers

Abstract

Nanoparticles with widely varying physical properties and origins (spherical versus irregular, synthetic versus biological, organic versus inorganic, flexible versus rigid, small versus large) have been previously noted to translocate across the cell plasma membrane. We have employed atomic force microscopy to determine if the physical disruption of lipid membranes, formation of holes and/or thinned regions, is a common mechanism of interaction between these nanoparticles and lipids. It was found that a wide variety of nanoparticles, including a cell penetrating pepide (MSI-78), a protein (TAT), polycationic polymers (PAMAM dendrimers, pentanol-core PAMAM dendrons, polyethyleneimine, and diethylaminoethyl-dextran), and two inorganic particles (Au-NH 2, SiO 2 -NH 2 ), can induce disruption, including the formation of holes, membrane thinning, and/or membrane erosion, in supported lipid bilayers.

Electrophysiological Characterization of Membrane Disruption by Nanoparticles

“…In other studies with silica nanospheres in aqueous buffer solution rather than cell culture medium, 50 nm aminated silica nanospheres were found to cause the formation of ∼100 nm holes in mica-supported phosphatidylcholine bilayers at nanomolar particle concentration. 13 Very recently, nonfunctionalized silica nanospheres with diameters of 37, 142, and 263 nm have been shown to induce 50% lysis of isolated red blood cells at concentrations respectively of 18 μg/mL (515 pM), 94 μg/mL (47 pM), and 307 μg/mL (25 pM). 32 Our investigation of asolectin bilayers, the sterol content of which is comparable to the red blood cell membrane, 22 demonstrates that 50 and 500 nm diameter silica nanospheres already cause a significant increase in bilayer current at a concentration of 8 pM, highlighting the sensitivity of electrophysiological characterization of membrane permeability.…”

Nanoparticle–membrane interactions

“…There are also other important NP characteristics that can be experimentally controlled and which can influence the NP-membrane adhesion beside the size. Cationic NPs, for example, are often cytotoxic due to their attractive interaction with negatively charged membranes that leads to their rapid internalisation [66,67]. On the other hand, anionic NPs are generally less cytotoxic but they can easily undergo protein fouling when exposed to biological media.…”

The effect of the protein corona on the interaction between nanoparticles and lipid bilayers

“…5 NPs can adhere to the lipid bilayer and cause changes in the lipid phase, 7 induce formation of lipid domains [8][9] or pores and extract lipids 10 inducing lipid bilayer disruption. [11][12] Physical chemical properties of NPs, 5,13 such as size, 4,11,[14][15] charge 12,16 and surface chemistry [17][18][19][20] are the main factors modulating NP-membrane interactions.…”