Cytotoxicity of CdSe and CdSe/ZnS nanoparticles has been investigated for different surface modifications such as coating with mercaptopropionic acid, silanization, and polymer coating. For all cases, quantitative values for the onset of cytotoxic effects in serum-free culture media are given. These values are correlated with microscope images in which the uptake of the particles by the cells has been investigated. Our data suggest that in addition to the release of toxic Cd(2+) ions from the particles also their surface chemistry, in particular their stability toward aggregation, plays an important role for cytotoxic effects. Additional patch clamp experiments investigate effects of the particles on currents through ion channels.

The re-engineering of biological protein pore scaffolds is a successful approach 12, 13 which has led, for example, to components for label-free biosensing [14][15][16][17] and portable genome sequencing 18, 19 . Creating completely new architectures with synthetic materials can offer greater design freedom and translate into more functions and applications [20][21][22][23][24][25][26] . A key challenge in the de-novo design of membrane channels is, however, to achieve an atomistically defined structure of predictable nanomechanical properties 3 because the traditional building blocks of polypeptides and organic polymers are highly flexible 2, 4 . DNA, by contrast, is known to fold into predetermined structures and is able to meet most the criteria required for creating synthetic channels [27][28][29][30][31][32][33] . Indeed, membrane-spanning DNA nanopores have been very 3" "recently built to feature a central hollow barrel which is open at both ends [5][6][7][8][9] . The barrel is composed of six hexagonally arranged, interconnected DNA duplexes that enclose a 2 nm-wide lumen with a length ranging from 17 to 42 nm. The innovative step was the inclusion of hydrophobic anchors 5, 7, 9 to insert the negatively charged pores into the hydrophobic bilayer membrane. While of novelty and considerable interest 34, 35 , the barrels do not exploit the full design flexibility offered by DNA nanotechnology and do not exhibit the higher-order functions of ion channels which can bind ligands, respond by nanomechanical opening, and select cargo for transport.We used the simple geometric shape of an open barrel as a starting point to rationally design a nanodevice that can regulate the flux of matter across a bilayer membrane.The aim of the first design step was reduce the pore height to approximate the bilayer thickness 36 and thereby avoid structural flexibility and potential leakiness 37 . A pore height of 7 nm (Fig. 1a, NP) was achieved using a six-helix-bundle architecture with six concatenated DNA strands, each of which connects two neighboring duplexes at their termini (Fig. 1b). This connectivity is drastically simpler than classical origami 38 based on cadnano software where oligonucleotides run through multiple duplexes and cause a minimum height of approx. 15 nm 5, 38 . Our design with connections at the duplex ends also avoids traditional internal cross-overs that cause structural deviations from parallel aligned duplexes 39 .The second step was to design a molecular gate that closes one barrel entrance but reopens the channel upon binding of a ligand. A origami plate has been previously used as a controllable lid for a DNA origami box 32 . But our molecular models supported by biophysical studies 37 suggest that the plate might be structurally too flexible and leaky 4" "to form a tight seal. As a solution, we designed a nanodevice that features in its closed state, NP-C (Fig. 1c), a simple "lock" strand which is bound closely to the entrance by hybridization to two docking sites. The sites are formed by th...

The state of the art technology for the study of ion channels is the patch clamp technique. Ion channels mediate electrical current flow, have crucial roles in cellular physiology, and are important drug targets. The most popular (whole cell) variant of the technique detects the ensemble current over the entire cell membrane. Patch clamping is still a laborious process, requiring a skilled experimenter to micromanipulate a glass pipette under a microscope to record from one cell at a time. Here we report on a planar, microstructured quartz chip for whole cell patch clamp measurements without micromanipulation or visual control. A quartz substrate of 200 microm thickness is perforated by wet etching techniques resulting in apertures with diameters of approximately 1 microm. The apertures replace the tip of glass pipettes commonly used for patch clamp recording. Cells are positioned onto the apertures from suspension by application of suction. Whole cell recordings from different cell types (CHO, N1E-115 neuroblastoma) are performed with microstructured chips studying K(+) channels and voltage gated Ca(2+) channels.