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Tumor-derived extracellular vesicles (TEVs) induce the epithelial-to-mesenchymal transition (EMT) in nonmalignant cells to promote invasion and cancer metastasis, representing a novel therapeutic target in a field severely lacking in efficacious antimetastasis treatments. However, scalable technologies that allow continuous, multiparametric monitoring for identifying metastasis inhibitors are absent. Here, the development of a functional phenotypic screening platform based on organic electrochemical transistors (OECTs) for real-time, noninvasive monitoring of TEV-induced EMT and screening of antimetastatic drugs is reported. TEVs derived from the triple-negative breast cancer cell line MDA-MB-231 induce EMT in nonmalignant breast epithelial cells (MCF10A) over a nine-day period, recapitulating a model of invasive ductal carcinoma metastasis. Immunoblot analysis and immunofluorescence imaging confirm the EMT status of TEV-treated cells, while dual optical and electrical readouts of cell phenotype are obtained using OECTs. Further, heparin, a competitive inhibitor of cell surface receptors, is identified as an effective blocker of TEV-induced EMT. Together, these results demonstrate the utility of the platform for TEV-targeted drug discovery, allowing for facile modeling of the transient drug response using electrical measurements, and provide proof of concept that inhibitors of TEV function have potential as antimetastatic drug candidates.

Cell membranes are integral to the functioning of the cell and are therefore key to drive fundamental understanding of biological processes for downstream applications. Here, we review the current state-of-the-art with respect to biomembrane systems and electronic substrates, with a view of how the field has evolved towards creating biomimetic conditions and improving detection sensitivity. Of particular interest are conducting polymers, a class of electroactive polymers, which have the potential to create the next step-change for bioelectronics devices. Lastly, we discuss the impact these types of devices could have for biomedical applications.

Cancer-derived exosomes (cEXOs) facilitate transfer of information between tumor and human primary stromal cells, favoring cancer progression. Although the mechanisms used during this information exchange are still not completely understood, it is known that binding is the initial contact established between cEXOs and cells. Hence, studying binding and finding strategies to block it are of great therapeutic value. However, such studies are challenging for a variety of reasons, including the need for human primary cell culture, the difficulty in decoupling and isolating binding from internalization and cargo delivery, and the lack of techniques to detect these specific interactions. In this work, we created a supported biomimetic stem cell membrane incorporating membrane components from human primary adipose-derived stem cells (ADSCs). We formed the supported membrane on glass and on multielectrode arrays to offer the dual option of optical or electrical detection of cEXO binding to the membrane surface. Using our platform, we show that cEXOs bind to the stem cell membrane and that binding is blocked when an antibody to integrin β1, a component of ADSC surface, is exposed to the membrane surface prior to cEXOs. To test the biological outcome of blocking this interaction, we first confirm that adding cEXOs to cultured ADSCs leads to the upregulation of vascular endothelial growth factor, a measure of proangiogenic activity. Next, when ADSCs are first blocked with anti-integrin β1 and then exposed to cEXOs, the upregulation of proangiogenic activity and cell proliferation are significantly reduced. This biomimetic membrane platform is the first cell-free label-free in vitro platform for the recapitulation and study of cEXO binding to human primary stem cells with potential for therapeutic molecule screening as it is compatible with scale-up and multiplexing.

We created a set of resources to enable research based on openly-available diffusion MRI (dMRI) data from the Healthy Brain Network (HBN) study. First, we curated the HBN dMRI data (N = 2747) into the Brain Imaging Data Structure and preprocessed it according to best-practices, including denoising and correcting for motion effects, susceptibility-related distortions, and eddy currents. Preprocessed, analysis-ready data was made openly available. Data quality plays a key role in the analysis of dMRI. To optimize QC and scale it to this large dataset, we trained a neural network through the combination of a small data subset scored by experts and a larger set scored by community scientists. The network performs QC highly concordant with that of experts on a held out set (ROC-AUC = 0.947). A further analysis of the neural network demonstrates that it relies on image features with relevance to QC. Altogether, this work both delivers resources to advance transdiagnostic research in brain connectivity and pediatric mental health, and establishes a novel paradigm for automated QC of large datasets., Scientific Data, 9 (1), ISSN:2052-4463

In case radionuclides (RN) enter the food chain and are incorporated by humans, they pose a possible health risk due to their radio- and chemotoxicity. To precisely assess the health risk after oral incorporation of RN with food and beverages and to apply effective decontamination methods, it is mandatory to understand the processes of RN biokinetics on both cellular and molecular scale. Within the joint research project RADEKOR: “Speciation and transfer of radionuclides in the human organism especially taking into account decorporation agents”, quantitative excretion analysis and biokinetic modeling of orally incorporated RN are performed. Additionally, these macroscopic investigations are combined with molecular speciation studies of RN in artificial fluids of the alimentary tract of humans and cytotoxicity studies with respective human and rat cell lines both in the absence and presence of decorporation agents. Aim of the project is to expand the knowledge of processes underlying RN interactions within the human alimentary tract on a cellular and molecular scale to establish a precise biokinetic model as well as to contribute to the development and improvement of nuclide specific decontamination methods. This joint project is funded by the German Federal Ministry of Education and Research (grant number 02NUK057). The funding period is from July 2020 to December 2023 and cooperation partners are: Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Technische Universität Dresden (TUD), Leibniz-Universität Hannover (LUH), Karlsruhe Institute of Technology (KIT), and VKTA - Radiation Protection, Analytics & Disposal (VKTA).

In case radionuclides (RN) enter the food chain and are incorporated by humans, they pose a possible health risk due to their radio- and chemotoxicity. To precisely assess the health risk after oral incorporation of RN with food and beverages and to apply effective decontamination methods, it is mandatory to understand the processes of RN biokinetics on both cellular and molecular scale. Within the joint research project “Speciation and transfer of radionuclides in the human organism especially taking into account decorporation agents (RADEKOR)”, quantitative excretion analysis and biokinetic modeling of orally incorporated RN are performed. Additionally, these macroscopic investigations are combined with molecular speciation studies of RN in artificial fluids of the alimentary tract of humans and cytotoxicity studies with respective human and rat cell lines both in the absence and presence of decorporation agents. Aim of the project is to expand the knowledge of processes underlying RN interactions within the human alimentary tract on a cellular and molecular scale to establish a precise biokinetic model as well as to contribute to the development and improvement of nuclide specific decontamination methods. This joint project is funded by the German Federal Ministry of Education and Research (grant number 02NUK057). The funding period is from July 2020 to December 2023 and cooperation partners are: Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Technische Universität Dresden (TUD), Leibniz-Universität Hannover (LUH), VKTA - Radiation Protection, Analytics & Disposal (VKTA), and Karlsruhe Institute of Technology (KIT).

Cancer-derived exosomes (cEXOs) facilitate transfer of information between tumor and human primary stromal cells, favoring cancer progression. Although the mechanisms used during this information exchange are still not completely understood, it is known that binding is the initial contact established between cEXOs and cells. Hence, studying binding and finding strategies to block it are of great therapeutic value. However, such studies are challenging for a variety of reasons, including the need for human primary cell culture, the difficulty in decoupling and isolating binding from internalization and cargo delivery, and the lack of techniques to detect these specific interactions. In this work, we created a supported biomimetic stem cell membrane incorporating membrane components from human primary adipose-derived stem cells (ADSCs). We formed the supported membrane on glass and on multielectrode arrays to offer the dual option of optical or electrical detection of cEXO binding to the membrane surface. Using our platform, we show that cEXOs bind to the stem cell membrane and that binding is blocked when an antibody to integrin β1, a component of ADSC surface, is exposed to the membrane surface prior to cEXOs. To test the biological outcome of blocking this interaction, we first confirm that adding cEXOs to cultured ADSCs leads to the upregulation of vascular endothelial growth factor, a measure of proangiogenic activity. Next, when ADSCs are first blocked with anti-integrin β1 and then exposed to cEXOs, the upregulation of proangiogenic activity and cell proliferation are significantly reduced. This biomimetic membrane platform is the first cell-free label-free in vitro platform for the recapitulation and study of cEXO binding to human primary stem cells with potential for therapeutic molecule screening as it is compatible with scale-up and multiplexing.

Emerging viruses will continue to be a threat to human health and wellbeing into the foreseeable future. The COVID-19 pandemic revealed the necessity for rapid viral sensing and inhibitor screening in mitigating viral spread and impact. Here, we present a platform that uses a label-free electronic readout as well as a dual capability of optical (fluorescence) readout to sense the ability of a virus to bind and fuse with a host cell membrane, thereby sensing viral entry. This approach introduces a hitherto unseen level of specificity by distinguishing fusion-competent viruses from fusion-incompetent viruses. The ability to discern between competent and incompetent viruses means that this device could also be used for applications beyond detection, such as screening antiviral compounds for their ability to block virus entry mechanisms. Using optical means, we first demonstrate the ability to recapitulate the entry processes of influenza virus using a biomembrane containing the viral receptor that has been functionalized on a transparent organic bioelectronic device. Next, we detect virus membrane fusion, using the same, label-free devices. Using both reconstituted and native cell membranes as materials to functionalize organic bioelectronic devices, configured as electrodes and transistors, we measure changes in membrane properties when virus fusion is triggered by a pH drop, inducing hemagglutinin to undergo a conformational change that leads to membrane fusion.