title: Polystyrene nanoparticle exposure induces ion-selective pores in lipid bilayers.
abstract: A diverse range of molecular interactions can occur between engineered nanomaterials (ENM) and biomembranes, some of which could lead to toxic outcomes following human exposure to ENM. In this study, we adapted electrophysiology methods to investigate the ability of 20nm polystyrene nanoparticles (PNP) to induce pores in model bilayer lipid membranes (BLM) that mimic biomembranes. PNP charge was varied using PNP decorated with either positive (amidine) groups or negative (carboxyl) groups, and BLM charge was varied using dioleoyl phospholipids having cationic (ethylphosphocholine), zwitterionic (phosphocholine), or anionic (phosphatidic acid) headgroups. Both positive and negative PNP induced BLM pores for all lipid compositions studied, as evidenced by current spikes and integral conductance. Stable PNP-induced pores exhibited ion selectivity, with the highest selectivity for K(+) (PK/PCl~8.3) observed when both the PNP and lipids were negatively charged, and the highest selectivity for Cl(-) (PK/PCl~0.2) observed when both the PNP and lipids were positively charged. This trend is consistent with the finding that selectivity for an ion in channel proteins is imparted by oppositely charged functional groups within the channel's filter region. The PK/PCl value was unaffected by the voltage-ramp method, the pore conductance, or the side of the BLM to which the PNP were applied. These results demonstrate for the first time that PNP can induce ion-selective pores in BLM, and that the degree of ion selectivity is influenced synergistically by the charges of both the lipid headgroups and functional groups on the PNP.
authors.affiliation: Department of Chemical Engineering and Material Science, Michigan State University, East Lansing, MI 48824, USA. negoda@msu.edu
authors.forename: Alexander
authors.initials: A
authors.lastname: Negoda
authors.forename: Kwang-Jin
authors.initials: KJ
authors.lastname: Kim
authors.forename: Edward D
authors.initials: ED
authors.lastname: Crandall
authors.forename: Robert M
authors.initials: RM
authors.lastname: Worden
mesh_terms: D002712:Chlorides / Q000737:chemistry; D007476:Ionophores / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008564:Membrane Potentials; D053758:Nanoparticles / Q000737:chemistry*; D010712:Phosphatidic Acids / Q000737:chemistry; D010767:Phosphorylcholine / Q000737:chemistry; D011137:Polystyrenes / Q000737:chemistry*; D011188:Potassium / Q000737:chemistry; D055672:Static Electricity
chemical_list: D002712:Chlorides; D007476:Ionophores; D008051:Lipid Bilayers; D010712:Phosphatidic Acids; D011137:Polystyrenes; D010767:Phosphorylcholine; D011188:Potassium
keywords: 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine; 1,2-dioleoyl-sn-glycero-3-phosphate; 1,2-dioleoyl-sn-glycero-3-phosphocholine; BLM; Biomembrane; COOH-PNP; DOEPC; DOPA; DOPC; E(rev); ENM; EPC; Electrophysiology; Engineered nanomaterials; Ion selectivity; LDH; Lipid bilayer; PA; PC; PNP; Pore; amidine-PNP; amidine-terminated polystyrene nanoparticles; bilayer lipid membranes; carboxyl-terminated PNP; engineered nanomaterials; ethylphosphocholine; lactic dehydrogenase; phosphatidic acid; phosphocholine; polystyrene nanoparticles; reversal potential