NanoE-Tox: New and in-depth database concerning ecotoxicity of nanomaterials

• Katre Juganson,
• Angela Ivask,
• Irina Blinova,
• Monika Mortimer and
• Anne Kahru

Beilstein J. Nanotechnol. 2015, 6, 1788–1804, doi:10.3762/bjnano.6.183

• interactions may cause cell membrane damage [13][46]. In most studies ζ-potential is used as an indication of the surface charge of ENMs and NPs are considered to be stable in aqueous suspension if the ζ-potential is greater than ±30 mV [47]. In NanoE-Tox database, ζ-potential was reported in 40% of the

Atomic force microscopy as analytical tool to study physico-mechanical properties of intestinal cells

• Christa Schimpel,
• Oliver Werzer,
• Eleonore Fröhlich,
• Gerd Leitinger,
• Markus Absenger-Novak,
• Birgit Teubl,
• Andreas Zimmer and
• Eva Roblegg

Beilstein J. Nanotechnol. 2015, 6, 1457–1466, doi:10.3762/bjnano.6.151

• parameters that reflect the plastic and/or elastic (deformation) behavior of the sample under load. For a mechanical response, which is ideally elastic, the indentation and retraction curve will be identical (overlap). Cells undergoing plastic deformations (i.e., the cell membrane is non-reversible distorted

• the cantilever got in contact with the sample. Due to strong adhesion forces (van der Waals forces), the tip snapped in contact with the cell membrane. When retracting the tip, adhesion was maintained until the cantilever-force overcame the pull-off force (also referred as adhesion force) [51]. Lowest

• permeation enhancer via altering of the cell membrane integrity [60]. Moreover, bile salts form micells in aequeous solutions, enhancing transport of foreign substances [61]. This clearly shows that further research activities (e.g.; liquid-state AFM imaging using simulated intestinal fluid) are required to

Protein corona – from molecular adsorption to physiological complexity

• Lennart Treuel,
• Dominic Docter,
• Michael Maskos and
• Roland H. Stauber

Beilstein J. Nanotechnol. 2015, 6, 857–873, doi:10.3762/bjnano.6.88

• confocal microscopy. In these experiments, all QDs were found to accumulate at the cell membrane within minutes after exposure. However, the kinetic analysis of this process showed characteristic times for QD association to the membrane to differ by more than one order of magnitude. Rate coefficients were

• also determined for internalization of NPs and varied less than a factor of 2. The combined interpretation of their data, allowed them to deduce that the overall uptake is controlled by the binding of the NP to the cell membrane. These findings will clearly help to design NPs for directed cellular

Hematopoietic and mesenchymal stem cells: polymeric nanoparticle uptake and lineage differentiation

• Ivonne Brüstle,
• Thomas Simmet,
• Gerd Ulrich Nienhaus,
• Katharina Landfester and
• Volker Mailänder

Beilstein J. Nanotechnol. 2015, 6, 383–395, doi:10.3762/bjnano.6.38

• localization of nanoparticles. Images were taken with a Leica SP5 II with a 60× oil immersion objective. The particle dye PMI was excited with the 488 nm laser, and the emission was collected at 510–540 nm. The cell membrane was stained with Cell Mask Orange according to the recommendations of the manufacturer

• , Figure S1. Particle uptake into hMSCs detected by cLSM after 24 h incubation with 300 µg/mL nanoparticles. (A) PS, (B) PS–COOH, (C) PLLA, (D) PLLA–Fe. The cell membrane is stained with CellMask Orange (red), nanoparticles are depicted in green, the cell nucleus is stained with DraQ5 and is pseudo-colored

Biological responses to nanoscale particles

• Reinhard Zellner

Beilstein J. Nanotechnol. 2015, 6, 380–382, doi:10.3762/bjnano.6.37

• techniques have been developed to unravel the chemical and molecular mechanistic details, as well as their biological consequences. Depending on whether a given cell spends energy during the uptake of nanoparticles or not, such uptake through the cell membrane is considered to be active or passive. While

Comparative evaluation of the impact on endothelial cells induced by different nanoparticle structures and functionalization

• Lisa Landgraf,
• Ines Müller,
• Peter Ernst,
• Miriam Schäfer,
• Christina Rosman,
• Isabel Schick,
• Oskar Köhler,
• Hartmut Oehring,
• Vladimir V. Breus,
• Thomas Basché,
• Carsten Sönnichsen,
• Wolfgang Tremel and
• Ingrid Hilger

Beilstein J. Nanotechnol. 2015, 6, 300–312, doi:10.3762/bjnano.6.28

• of different nanoparticles by endothelial cells depends mainly on the surface charge. Microscopical analysis of nanoparticle uptake after 24 h of incubation: (a) SVEC4-10 after treatment with quantum dots (QDs). The QDs are indicated in red (red fluorescence), the cell membrane in green and the

The effect of surface charge on nonspecific uptake and cytotoxicity of CdSe/ZnS core/shell quantum dots

• Vladimir V. Breus,
• Anna Pietuch,
• Marco Tarantola,
• Thomas Basché and
• Andreas Janshoff

Beilstein J. Nanotechnol. 2015, 6, 281–292, doi:10.3762/bjnano.6.26

• during 2–4 hours of exposure of cells to CA–QDs. A series of frames shown in Supporting Information File 1, Figure S3 illustrates the CA–QD-induced endosome shaping from the MDCKII cell membrane into the cellular interior after 2 h of interaction. The fluorescent spot corresponding to the formed vesicle

Tailoring the ligand shell for the control of cellular uptake and optical properties of nanocrystals

• Johannes Ostermann,
• Christian Schmidtke,
• Christopher Wolter,
• Jan-Philip Merkl,
• Hauke Kloust and
• Horst Weller

Beilstein J. Nanotechnol. 2015, 6, 232–242, doi:10.3762/bjnano.6.22

• to enhance the cellular uptake, due to the attractive interaction with the negatively charged cell membrane [35][36]. Therefore, control over the surface chemistry is crucial to study the nanocontainers behavior in vitro and in vivo. Figure 7 shows possible functionalization of PI-b-PEG prior to the

• samples, bearing the amino functions showed no unspecific interaction with the cell membrane, which qualifies the nanocontainers in a first step as versatile tools for specific targeting, since no unspecific background has to be expected. Figure 10 shows exemplarily the confocal microscopy images for the

Mechanical properties of MDCK II cells exposed to gold nanorods

• Anna Pietuch,
• Bastian Rouven Brückner,
• David Schneider,
• Marco Tarantola,
• Christina Rosman,
• Carsten Sönnichsen and
• Andreas Janshoff

Beilstein J. Nanotechnol. 2015, 6, 223–231, doi:10.3762/bjnano.6.21

• periphery of the nucleus. However, we never observed particles inside the nucleus. On some TEM images, particles are located in close proximity to the inner cell membrane [13]. In essence, we observed uptake and aggregation of CTAB coated particles almost immediately after addition, at least within a few

• of nanomedicine results from both their therapeutic and diagnostic potential based on their tuneable size in the range of 1–100 nm [1][2][3][4][5]. Being in the size-regime of cellular components such as DNA and proteins, nanoparticles are capable to overcome native dielectric barriers like the cell

• membrane rendering them prime candidates for multifunctional carriers [6][7][8]. Potential applications encompass selective drug delivery, photothermal therapy, reporters for biosensors and the use as contrast agents [5][9]. Targets can be addressed specifically by functionalization of the particle surface

Caveolin-1 and CDC42 mediated endocytosis of silica-coated iron oxide nanoparticles in HeLa cells

• Nils Bohmer and
• Andreas Jordan

Beilstein J. Nanotechnol. 2015, 6, 167–176, doi:10.3762/bjnano.6.16

• numbers were observed, which confirmed no severe impact of the treatment on cell viability within the observation period. Quantitative iron analysis For quantitative determination of iron, which was taken up by cells and not attached to the plastic surface or to the outer cell membrane, cells were washed

• compositions via the Dharmacon SMARTpool® technology. As described above, cells were incubated with PEGylated SPIONs for 24 h and iron content per cell was determined. To distinguish between nanoparticles inside the cells and nanoparticles, which are attached to the outer cell membrane, control experiments at

• of SCIONs by HeLa cells. This could be an indication for an unknown, alternative uptake mechanism, which is dependent on Caveolin-1 but independent from Dynamin 2. Because it is known, that Dynamin 2 plays an important role in the constriction of caveolae-coated vesicles from the inner cell membrane

Increasing throughput of AFM-based single cell adhesion measurements through multisubstrate surfaces

• Miao Yu,
• Nico Strohmeyer,
• Jinghe Wang,
• Daniel J. Müller and
• Jonne Helenius

Beilstein J. Nanotechnol. 2015, 6, 157–166, doi:10.3762/bjnano.6.15

• with the unbinding of either single or clustered CAMs and can be characterized as either rupture or tether events [15][17][20]. The analysis of these unbinding events may be used to characterize the strength of single bonds and cell membrane properties [17][24][25]. Examples of the utility of SCFS

• . Rupture events are recorded when the CAM–ligand bond of a cytoskeleton-linked CAM fails. Tether events are recorded when a membrane tether is extruded from the cell membrane with the CAM at its tip (tethers). In the latter case, attachment of the CAM to the cytoskeleton is either too weak to resist the

Synthesis of boron nitride nanotubes and their applications

• Saban Kalay,
• Zehra Yilmaz,
• Ozlem Sen,
• Melis Emanet,
• Emine Kazanc and
• Mustafa Çulha

Beilstein J. Nanotechnol. 2015, 6, 84–102, doi:10.3762/bjnano.6.9

• block ATP. They concluded that the PLL–BNNTs accumulation occurred in the cell membrane with energy dependent pathways. At a concentration of up to 10 µg/mL, the PLL–BNNTs exhibited no evidence of apoptosis, necrosis and membrane permeabilization [79]. Danti et al. investigated the cellular uptake of

• demonstrated that a low electric field was adequate for electroporation. The BNNTs acted as mediators for electroporation as they interacted with the cell membrane. These experimental findings indicated that the BNNTs are promising tools for drug and gene delivery using electroporation [87]. A theoretical

Mammalian cell growth on gold nanoparticle-decorated substrates is influenced by the nanoparticle coating

• Christina Rosman,
• Sebastien Pierrat,
• Marco Tarantola,
• David Schneider,
• Eva Sunnick,
• Andreas Janshoff and
• Carsten Sönnichsen

Beilstein J. Nanotechnol. 2014, 5, 2479–2488, doi:10.3762/bjnano.5.257

• results to cell growth on bare substrates. The study utilized three different surface coatings because the particle-bound molecules (stabilizing agents) are expected to promote diverse interactions with the cell membrane [21][22]. One coating consists of cetyltrimethylammonium bromide (CTAB), which is a

• translucent that the scattered light from the particles below the membrane can pass through and is visible (Figure 1B: cortical membrane of Figure 1A enlarged). The membrane tightly covers the particles, which is verified by a scanning electron microscopy image in Figure 1C. When the cell membrane retracts, a

• impact on the cells compared to growth on bare substrates, since the particle bound molecules (stabilizing agents) are expected to promote diverse interactions with the cell membrane [21][22]. One coating was cetyltrimethylammonium bromide (CTAB), which is a relatively cytotoxic cationic surfactant [11

Intake of silica nanoparticles by giant lipid vesicles: influence of particle size and thermodynamic membrane state

• Florian G. Strobl,
• Florian Seitz,
• Christoph Westerhausen,
• Armin Reller,
• Adriano A. Torrano,
• Christoph Bräuchle,
• Achim Wixforth and
• Matthias F. Schneider

Beilstein J. Nanotechnol. 2014, 5, 2468–2478, doi:10.3762/bjnano.5.256

• possessing such a machinery [13]. This indicates that endocytosis-like particle uptake can be driven by physical interactions between cargo and cell membrane. The investigation of simplified model systems thus offers a possibility for an understanding of these processes on a theoretical physical base. In

• interactions and possible thermodynamic changes of the lipid membrane, which can result in drastic alterations of its physical properties (e.g., bending stiffness, permeability and spontaneous curvature). Even though the model system that was investigated here is quite distinct from a real cell membrane we

• −20 mV for HeLa cells and −30 mV for red blood cells were measured [49]. The dotted curve in Figure 4 shows the expected electrostatic force between a cationic particle with ζ = +30 mV and a cell membrane with ζ = −30 mV in a medium with an ionic strength of I = 160 mM. The physical forces in this

Proinflammatory and cytotoxic response to nanoparticles in precision-cut lung slices

• Stephanie Hirn,
• Nadine Haberl,
• Kateryna Loza,
• Matthias Epple,
• Wolfgang G. Kreyling,
• Barbara Rothen-Rutishauser,
• Markus Rehberg and
• Fritz Krombach

Beilstein J. Nanotechnol. 2014, 5, 2440–2449, doi:10.3762/bjnano.5.253

• staining, and WST-1 assay. As LDH is present in the cytoplasm of cells, detection of LDH in the culture medium of PCLS indicates a loss of cell membrane integrity. Therefore, LDH release is a direct measure of a cytotoxic response or an indirect measure of cell viability. As displayed in Figure 1, the LDH

Nanoparticle interactions with live cells: Quantitative fluorescence microscopy of nanoparticle size effects

• Li Shang,
• Karin Nienhaus,
• Xiue Jiang,
• Linxiao Yang,
• Katharina Landfester,
• Volker Mailänder,
• Thomas Simmet and
• G. Ulrich Nienhaus

Beilstein J. Nanotechnol. 2014, 5, 2388–2397, doi:10.3762/bjnano.5.248

• . By using spinning disk confocal microscopy in combination with quantitative image analysis, we studied the time courses of NP association with the cell membrane and subsequent internalization. NPs with diameters of less than 10 nm were observed to accumulate at the plasma membrane before being

• machinery in order to trigger the subsequent internalization. Keywords: cell membrane; endocytosis; fluorescence microscopy; nanoparticle; size effect; Introduction Understanding the interaction between engineered nanomaterials and living matter has attracted increasing attention in recent years

• internalization machinery involved, different endocytic mechanisms are utilized. Most cells are capable of pinocytosis (drinking by cells), in which particles of up to several hundred nanometers can be internalized [11]. In this process, an invagination forms in the cell membrane. Typically, the inward budding

Nanobioarchitectures based on chlorophyll photopigment, artificial lipid bilayers and carbon nanotubes

• Marcela Elisabeta Barbinta-Patrascu,
• Stefan Marian Iordache,
• Ana Maria Iordache,
• Nicoleta Badea and
• Camelia Ungureanu

Beilstein J. Nanotechnol. 2014, 5, 2316–2325, doi:10.3762/bjnano.5.240

• . [49] pointed out that cell membrane damage resulting from direct contact with carbon nanotubes is the most plausible mechanism leading to bacterial cell death. Our results showed that small amounts of SWCNTs were enough to achieve high antimicrobial potency (see samples V3 and V4). The cholesterol

Coating with luminal gut-constituents alters adherence of nanoparticles to intestinal epithelial cells

• Heike Sinnecker,
• Katrin Ramaker and
• Andreas Frey

Beilstein J. Nanotechnol. 2014, 5, 2308–2315, doi:10.3762/bjnano.5.239

• – directly on the cell membrane. This interaction-type can be abolished by treating the particles with proteins (“passivation” of particle surface). Coating of particles with constituents of the intestinal fluid, on the other hand, may result in more complex attachment mechanisms. The intestinal fluid is a

Imaging the intracellular degradation of biodegradable polymer nanoparticles

• Anne-Kathrin Barthel,
• Martin Dass,
• Melanie Dröge,
• Jens-Michael Cramer,
• Daniela Baumann,
• Markus Urban,
• Katharina Landfester,
• Volker Mailänder and
• Ingo Lieberwirth

Beilstein J. Nanotechnol. 2014, 5, 1905–1917, doi:10.3762/bjnano.5.201

• the cell membrane are recognized by the overlay of red- and green-stained regions (cell membrane and PLLA nanoparticles, respectively) and are displayed as yellow pixels in the CLSM overlay images. However, there are no prominent attachments of the particles to the cellular membrane and only rarely

• showing the relative fluorescence intensity of the cells for different residence times. CLSM images of cells treated with PLLA/magnetite particles; incubation time: 24 h; pictures taken at specified times after particle addition: A) 24 h, B) 48 h, C) 72 h, D) 5 d, E) 7 d, and F) 14 days. Red: cell

• membrane; Green: PLLA nanoparticles. TEM bright field micrographs of a dispersion of magnetite-decorated PLLA nanoparticles prepared by drop casting and subsequent carbon evaporation (A) and by high pressure freezing (HPF) followed by freeze substitution and microtomy (B). The inset of B shows the

Carbon-based smart nanomaterials in biomedicine and neuroengineering

• Antonina M. Monaco and
• Michele Giugliano

Beilstein J. Nanotechnol. 2014, 5, 1849–1863, doi:10.3762/bjnano.5.196

• the spontaneous extracellular electrical activity in a murine neuronal cell line, which yielded results in good agreement with recordings made by means of conventional MEAs (Figure 5). Single-spin NV-NDs embedded in an artificial lipid bilayer [136] and in a real cell membrane, in which there is a

Influence of surface-modified maghemite nanoparticles on in vitro survival of human stem cells

• Michal Babič,
• Daniel Horák,
• Lyubov L. Lukash,
• Tetiana A. Ruban,
• Yurii N. Kolomiets,
• Svitlana P. Shpylova and
• Oksana A. Grypych

Beilstein J. Nanotechnol. 2014, 5, 1732–1737, doi:10.3762/bjnano.5.183

• cellular uptake of the magnetic nanoparticles and enhance their specific targeting effect, surface functionalization has to be employed to coat the nanoparticle surface with ligands that could specifically interact with the receptors overexpressed in the cell membrane. While the size of the dry

In vitro and in vivo interactions of selected nanoparticles with rodent serum proteins and their consequences in biokinetics

• Wolfgang G. Kreyling,
• Stefanie Fertsch-Gapp,
• Martin Schäffler,
• Blair D. Johnston,
• Nadine Haberl,
• Christian Pfeiffer,
• Jörg Diendorf,
• Carsten Schleh,
• Stephanie Hirn,
• Manuela Semmler-Behnke,
• Matthias Epple and
• Wolfgang J. Parak

Beilstein J. Nanotechnol. 2014, 5, 1699–1711, doi:10.3762/bjnano.5.180

• twenty-four hours the viability of the PCLS was tested by lactate dehydrogenase (LDH) analysis for cell membrane damage and a WST-1 assay for mitochondrial activity in the cell culture supernatant as well as the release of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin

• increased in PCLS from rats treated with six-month old, 250 µg AgNP. But this increase was not statistically significant. This indicates that dissolved/dissociated Ag species which had been released from AgNP damaged the cell membrane of PCLS more than the Ag+ ions from silver acetate. However

Different endocytotic uptake mechanisms for nanoparticles in epithelial cells and macrophages

• Dagmar A. Kuhn,
• Dimitri Vanhecke,
• Benjamin Michen,
• Fabian Blank,
• Peter Gehr,
• Alke Petri-Fink and
• Barbara Rothen-Rutishauser

Beilstein J. Nanotechnol. 2014, 5, 1625–1636, doi:10.3762/bjnano.5.174

• interaction of the responsible receptors on the cell surface and the ligands. Macropinocytosis, which is also actin-driven, forms protrusions at the outer cell membrane which then again fuse with the cell membrane by taking up larger fragments or debris [14]. Clathrin-mediated endocytosis is very well studied

• consisting of transmembrane receptors and cytosolic proteins, such as clathrin and the AP2 adaptor complex [20]. On the other hand, caveolin-mediated endocytosis is responsible for the homeostasis of cholesterol [20]. The static structures of caveolae form flask-shaped invaginations in the cell membrane

• , fluorescently labelled transferrin can be used to investigate clathrin-mediated endocytosis [32][41][42]. Caveolae and lipid raft internalizations are known to be inhibited by nystatin, filipin and methyl-β-cyclodextrin (mβcd) through depletion of the cholesterol from the cell membrane by forming inclusion

Precise quantification of silica and ceria nanoparticle uptake revealed by 3D fluorescence microscopy

• Adriano A. Torrano and
• Christoph Bräuchle

Beilstein J. Nanotechnol. 2014, 5, 1616–1624, doi:10.3762/bjnano.5.173

• microscopy. One emission channel is reserved for the plasma membrane and the other one for the nanoparticles. This means that cell membrane and particles must be fluorescently labeled with spectrally separable markers. The two image stacks acquired can then be processed by Particle_in_Cell-3D. Once the

• an enlarged transition region between extra- and intracellular spaces. It is much wider than the real cell membrane. The accuracy of the cell segmentation strategy and the typical thickness of the enlarged membrane region were studied by comparing the results achieved with Particle_in_Cell-3D with

• growth. Before addition to cells, the solution was vortexed for 10 s, treated in an ultrasonic bath for 10 min and vortexed again for 10 s. After the incubation time, and just before measurements, the cell membrane was stained with a solution of 10 µg·mL−1 wheat germ agglutinin, Alexa Fluor® 488 (Life

In vitro interaction of colloidal nanoparticles with mammalian cells: What have we learned thus far?

• Moritz Nazarenus,
• Qian Zhang,
• Mahmoud G. Soliman,
• Pablo del Pino,
• Beatriz Pelaz,
• Susana Carregal-Romero,
• Joanna Rejman,
• Barbara Rothen-Rutishauser,
• Martin J. D. Clift,
• Reinhard Zellner,
• G. Ulrich Nienhaus,
• James B. Delehanty,
• Igor L. Medintz and
• Wolfgang J. Parak

Beilstein J. Nanotechnol. 2014, 5, 1477–1490, doi:10.3762/bjnano.5.161

• which the goal is to deliver something to the cytosol. Getting stuck inside intracellular vesicles is redundant to the purpose of these applications. However, in contrast to endocytosis as described so far, studies exist in which it is claimed that NPs can directly translocate through the cell membrane

• kinetics [103]. Larger NPs (smaller than 60–70 nm) are internalized with lower kinetics to the extent that they are largely associated to the cell membrane over the time courses that see an intake of smaller NPS [62]. This has also been shown in fixed, permeabilized cells (to eliminate cell uptake

• fibers with high aspect ratios [100]. Flattening of NPs has been used, for example, to reduce NP uptake by cells in a way that flat NPs just adhere to the plasma cell membrane like a “backpack”, without being internalized, in contrast to spherical NPs that are readily incorporated [113][114]. Concerning