Biology subjects

Umek, P.

Publications and source records attributed to Umek, P..

4 recordsLinked to original sources

bioRxiv2024

Binucleated cell formation and oncogene expression after particulate matter exposure is preceded by microtubule disruption, dysregulated cell cycle, prolonged mitosis, and septin binding

Several biopersistent high aspect ratio nanomaterials show pronounced pathogenic effects, from chronic lung inflammation and fibrosis to cancer. For example, asbestos fibers are classified as carcinogens, whereas the carcinogenicity of highly inflammatory multi-wall carbon nanotubes (MWCNTs), and TiO2 nanomaterials is still being evaluated. The exact early mechanisms of their pathogenicity towards inflammation and cancer remains uncertain, but it is likely not due to genotoxic or mutagenic activity. A proposed early mode of action that might lead to the formation of cancerous cells for asbestos fibers is the formation of binucleated and multinucleated cells, resulting in genetic instability. Here, we show that two high aspect ratio nanomaterials, MWCNTs and TiO2 nanotubes, which both induce chronic lung inflammation, induce very different cancer-related changes in vitro. TiO2 nanotubes - but not low aspect-ratio nanocubes of the same crystalline structure - disrupt microtubule organization and prolong mitosis, as well as deform nuclear shape, induce the formation of binucleated cells, and downregulate the tumour suppressor protein p53, whereas only the MWCNTs activate the stimulator of the interferon genes (STING) pathway, a hallmark of lung cancer. The observed differences in cellular responses to different high aspect ratio materials imply the need for assessing each nanomaterial individually with a broad range of tests rather than relying solely on a single marker or pathway, or even morphological or bulk chemical properties to infer possible carcinogenic properties.

cancer biology↗

bioRxiv2021

Controlled Fluorescent Labelling of Metal Oxide Nanoparticles for Artefact-free Live Cell Microscopy

Nanotechnologies hold great promise for various applications. To predict and guarantee the safety of novel nanomaterials, it is essential to understand their mechanism of action in an organism, causally connecting adverse outcomes with early molecular events. They are best investigated using non-invasive advanced optical methods, such as high-resolution live-cell fluorescence microscopy, which require stable labelling of nanoparticles with fluorescent dyes. When performed inadequately, unbound fluorophores and inadvertently altered chemical and physical properties of the nanoparticles can, however, result in experimental artefacts and erroneous conclusions. To prevent such unintentional errors, we here describe a minimal combination of experimental methods to enable artefact-free fluorescent labelling of metal-oxide nanoparticles - the largest subpopulation of nanoparticles by industrial production and applications - and demonstrate its application in the case of TiO2 nanotubes. We 1) characterize potential changes of the nanoparticles surface charge and morphology that might occur during labelling, and 2) assess stable binding of the fluorescent dye to nanomaterial, which ensures correct nanoparticle localization. Together, these steps warrant the reliability and reproducibility of advanced optical tracking, which is necessary to explore nanomaterials mechanism of action and will foster widespread and safe use of new nanomaterials. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/440400v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@358ffborg.highwire.dtl.DTLVardef@7faaecorg.highwire.dtl.DTLVardef@1ae7fb3org.highwire.dtl.DTLVardef@141c4b5_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2020

Towards predictive nanotoxicology: from roundabout of molecular events to chronic inflammation prediction

Nanomaterial-induced diseases cannot be reliably predicted because of the lack of clearly identified causal relationships, in particular between acute exposures and chronic symptoms. By applying advanced microscopies and omics to in vitro and in vivo systems, together with in silico molecular modelling, we have here determined that the long-lasting response to a single exposure originates in the counteracting of a newly discovered nanomaterial quarantining and nanomaterial cycling among different lung cell types. This allows us to predict the nanomaterial-induced spectrum of lung inflammation using only in vitro measurements and in silico modelling. Besides its profound implications for cost-efficient animal-free predictive toxicology, our work also paves the way to a better mechanistic understanding of nanomaterial- induced cancer, fibrosis, and other chronic diseases.

molecular biology↗

bioRxiv2017

Photocatalytic disinfection of surfaces with copper doped TiO2 nanotube coatings illuminated by ceiling mounted fluorescent lights

High economic burden is associated with foodborne illnesses. Different disinfection methods are therefore employed in food processing industry; such as use of ultraviolet light or usage of surfaces with copper-containing alloys. However, all the disinfection methods currently in use have some shortcomings. Here we show that copper doped TiO2 nanotubes deposited on existing surfaces and illuminated with ceiling mounted fluorescent lights or additional low power light emitting diodes can be employed for an economical and permanent disinfection of surfaces.\n\nWe deposited the nanotubes on various surfaces: polyethylene terephatlate, polystyrene, and aluminum oxide, where they could withstand repeated washings with neutral, alkaline or acidic medium. Here we show that the polymer surfaces coated with the nanotubes and innoculated with 107 bacteria, illuminated with ceiling mounted fluorescent lights retard the growth of Listeria Innocua by up to 99% in seven hours of exposure to the fluorescent lights, compared to a control surface. The disinfection properties of the surfaces depend mainly on the temperature difference of the surface and the dew point, where for maximum effectiveness of the photocatalytic effect the difference should be at least 2.5 degrees celsius.\n\nUsage of one dimensional nanomaterials, such as TiO2 nanotubes, offers a promising low cost alternative to current disinfection methods, since illumination of surfaces with common fluorescent lights is sufficient to photo-excite the nanotubes, which sequentially produce microbicidal hydroxyl radicals. Future use of such surfaces with antibacterial nano-coating and resulting sterilizing effect holds promise for such materials to be used in different environments or in better control of critical control points in food production as well as an improved biosecurity during the food manufacturing process.

bioengineering↗