Native silica nanoparticles are powerful membrane disruptors

Silica nanoparticles are under development for intracellular drug delivery applications but can also have cytotoxic effects including cell membrane damage. In this study, we investigated the interactions of silica nanospheres of different size, surface chemistry and biocoating with membranes of phosphatidylcholine lipids. In liposome leakage assays many, but not all, of these nanoparticles induced dose-dependent dye leakage, indicative of membrane perturbation. It was found that 200 and 500 nm native-silica, aminated and carboxylated nanospheres induce near-total dye release from zwitterionic phosphatidylcholine liposomes at a particle/liposome ratio of ~1, regardless of their surface chemistry, which we interpret as particle-supported bilayer formation following a global rearrangement of the vesicular membrane. In contrast, 50 nm diameter native-silica nanospheres did not induce total dye leakage below a particle/liposome ratio of ~8, whereas amination or carboxylation, respectively, strongly reduced or prevented dye release. We postulate that for the smaller nanospheres, strong silica-bilayer interactions are manifested as bilayer engulfement of membrane-adsorbed particles, with localized lipid depletion eventually leading to collapse of the vesicular membrane. Protein coating of the particles considerably reduced dye leakage and lipid bilayer coating prevented dye release all together, while the inclusion of 33% anionic lipids in the liposomes reduced dye leakage for both native-silica and aminated surfaces. These results, which are compared with the effect of polystyrene nanoparticles and other engineered nanomaterials on lipid bilayers, and which are discussed in relation to nanosilica-induced cell membrane damage and cytotoxicity, indicate that a native-silica nanoparticle surface chemistry is a particularly strong membrane interaction motif

Belousov-Zhabotinsky droplet mixing on-chip for chemical computing applications

Without an imposed physical structure, even the most complex chemistries are limited in their ability to process information. For example, the Belousov-Zhabotinsky (BZ) oscillating reaction has been shown to have information procession potential, but only if structure is imposed e.g. using physical barriers or light-sensitive catalysts. Recently, separated BZ droplets in oil have been investigated. Another option for aqueous/oil systems is to add lipid into the oil, which self-assembles into a monolayer at the phase boundary. If the lipid-stabilised droplets are brought into contact, a bilayer is formed, separating the BZ droplets into compartments. This technique is more flexible than other methods of imparting structure, allowing for the creation of droplet arrays inspired by biological neuronal networks

A low-noise transimpedance amplifier for BLM-based ion channel recording

High-throughput screening (HTS) using ion channel recording is a powerful drug discovery technique in pharmacology. Ion channel recording with planar bilayer lipid membranes (BLM) is scalable and has very high sensitivity. A HTS system based on BLM ion channel recording faces three main challenges: (i) design of scalable microfluidic devices; (ii) design of compact ultra-low-noise transimpedance amplifiers able to detect currents in the pA range with bandwidth >10 kHz; (iii) design of compact, robust and scalable systems that integrate these two elements. This paper presents a low-noise transimpedance amplifier with integrated A/D conversion realized in CMOS 0.35 µm technology. The CMOS amplifier acquires currents in the range ±200 pA and ±20 nA, with 100 kHz bandwidth while dissipating 41 mW. An integrated digital offset compensation loop balances any voltage offsets from Ag/AgCl electrodes. The measured open-input input-referred noise current is as low as 4 fA/Root Hz at ±200 pA range. The current amplifier is embedded in an integrated platform, together with a microfluidic device, for current recording from ion channels. Gramicidin-A, alpha-haemolysin and KcsA potassium channels have been used to prove both the platform and the current-to-digital converter

Recognition Pliability Is Coupled to Structural Heterogeneity: A Calmodulin Intrinsically Disordered Binding Region Complex

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