title: Direct proof of spontaneous translocation of lipid-covered hydrophobic nanoparticles through a phospholipid bilayer.
abstract: Hydrophobic nanoparticles introduced into living systems may lead to increased toxicity, can activate immune cells, or can be used as nanocarriers for drug or gene delivery. It is generally accepted that small hydrophobic nanoparticles are blocked by lipid bilayers and accumulate in the bilayer core, whereas big nanoparticles can only penetrate cells through slow energy-dependent processes, such as endocytosis, lasting minutes. In contrast to expectations, we demonstrate that lipid-covered hydrophobic nanoparticles may translocate through lipid membranes by direct penetration within milliseconds. We identified the threshold size for translocation: nanoparticles with diameters smaller than 5 nm stay trapped in the bilayer, whereas those with diameters larger than 5 nm insert into the bilayer, opening pores in the bilayer. The direct proof of this size-dependent translocation was provided by an in situ observation of a single event of a nanoparticle quitting the bilayer. This was achieved with a specially designed microfluidic device combining optical fluorescence microscopy with simultaneous electrophysiological measurements. A quantitative analysis of the kinetic pathway of a single nanoparticle translocation event demonstrated that the translocation is irreversible and that the nanoparticle can translocate only once. This newly discovered one-way translocation mechanism provides numerous opportunities for biotechnological applications, ranging from targeted biomaterial elimination and/or delivery to precise and controlled trapping of nanoparticles.
authors.affiliation: Departament d'Enginyeria Química, Universitat Rovira i Virgili, 26 Avinguda dels Països Catalans, 43007 Tarragona, Spain.
authors.forename: Yachong
authors.identifier: 0000-0001-6821-0483
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Geneva, 30 quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Terazzi
authors.affiliation: Experimental Physics, Universität des Saarlandes, 66123 Saarbrücken, Germany.
authors.forename: Ralf
authors.identifier: 0000-0002-4180-0819
authors.initials: R
authors.lastname: Seemann
authors.affiliation: Experimental Physics, Universität des Saarlandes, 66123 Saarbrücken, Germany.
authors.forename: Jean Baptiste
authors.initials: JB
authors.lastname: Fleury
authors.affiliation: Departament d'Enginyeria Química, Universitat Rovira i Virgili, 26 Avinguda dels Països Catalans, 43007 Tarragona, Spain.
authors.forename: Vladimir A
authors.identifier: 0000-0003-2086-4271
authors.initials: VA
authors.lastname: Baulin
mesh_terms: D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D010743:Phospholipids
keywords: Lipid bilayers; microfluidics; nanoparticles; translocation dynamics