Interfacing artificial devices with the human brain is the central goal of neurotechnology. Yet, our imaginations are often limited by currently available paradigms and technologies. Suggestions for brain-machine interfaces have changed over time, along with the available technology. Mechanical levers and cable winches were used to move parts of the brain during the mechanical age. Sophisticated electronic wiring and remote control have arisen during the electronic age, ultimately leading to plug-and-play computer interfaces. Nonetheless, our brains are so complex that these visions, until recently, largely remained unreachable dreams. The general problem, thus far, is that most of our technology is mechanically and/or electrically engineered, whereas the brain is a living, dynamic entity. As a result, these worlds are difficult to interface with one another. Nanotechnology, which encompasses engineered solid-state objects and integrated circuits, excels at small length scales of single to a few hundred nanometers and, thus, matches the sizes of biomolecules, biomolecular assemblies, and parts of cells. Consequently, we envision nanomaterials and nanotools as opportunities to interface with the brain in alternative ways. Here, we review the existing literature on the use of nanotechnology in brain-machine interfaces and look forward in discussing perspectives and limitations based on the authors' expertise across a range of complementary disciplines─from neuroscience, engineering, physics, and chemistry to biology and medicine, computer science and mathematics, and social science and jurisprudence. We focus on nanotechnology but also include information from related fields when useful and complementary.
- Klíčová slova
- Nanoneuro interface, brain-on-a-chip, brain−machine interfaces, control of ion channels, deep brain stimulation, electrode arrays, extracellular recordings, nanostructured interface, neuro-implants, neuronal communication,
- MeSH
- lidé MeSH
- mozek * fyziologie MeSH
- nanostruktury chemie MeSH
- nanotechnologie * metody MeSH
- rozhraní mozek-počítač * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
Quantitative genomic mapping of DNA damage may provide insights into the underlying mechanisms of damage and repair. Sequencing based approaches are bound to the limitations of PCR amplification bias and read length which hamper both the accurate quantitation of damage events and the ability to map them to structurally complex genomic regions. Optical Genome mapping in arrays of parallel nanochannels allows physical extension and genetic profiling of millions of long genomic DNA fragments, and has matured to clinical utility for characterization of complex structural aberrations in cancer genomes. Here we present a new mapping modality, Repair-Assisted Damage Detection - Optical Genome Mapping (RADD-OGM), a method for single-molecule level mapping of DNA damage on a genome-wide scale. Leveraging ultra-long reads to assemble the complex structure of a sarcoma cell-line genome, we mapped the genomic distribution of oxidative DNA damage, identifying regions more susceptible to DNA oxidation. We also investigated DNA repair by allowing cells to repair chemically induced DNA damage, pinpointing locations of concentrated repair activity, and highlighting variations in repair efficiency. Our results showcase the potential of the method for toxicogenomic studies, mapping the effect of DNA damaging agents such as drugs and radiation, as well as following specific DNA repair pathways by selective induction of DNA damage. The facile integration with optical genome mapping enables performing such analyses even in highly rearranged genomes such as those common in many cancers, a challenging task for sequencing-based approaches.
- Klíčová slova
- CNV, Cancer genomes, Cytogenetics, DNA damage, DNA repair, Long-reads, Nanochannels, OGM, Osteosarcoma, Oxidative damage, RADD, S.V., Single molecule, Toxicogenomics,
- MeSH
- bromičnany toxicita MeSH
- lidé MeSH
- mapování chromozomů * přístrojové vybavení metody MeSH
- mikrofluidní analytické techniky * přístrojové vybavení metody MeSH
- nádorové buněčné linie MeSH
- nanotechnologie * přístrojové vybavení metody MeSH
- oprava DNA genetika MeSH
- oxidační stres účinky léků genetika MeSH
- poškození DNA * genetika MeSH
- regulace genové exprese MeSH
- stanovení celkové genové exprese MeSH
- toxikogenetika * přístrojové vybavení metody MeSH
- variabilita počtu kopií segmentů DNA MeSH
- zobrazení jednotlivé molekuly * přístrojové vybavení metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- bromičnany MeSH
- potassium bromate MeSH Prohlížeč
Understanding the function of a biomolecule hinges on its 3D conformation or secondary structure. Chirally sensitive, optically active techniques based on the differential absorption of UV-vis circularly polarized light excel at rapid characterisation of secondary structures. However, Raman spectroscopy, a powerful method for determining the structure of simple molecules, has limited capacity for structural analysis of biomolecules because of intrinsically weak optical activity, necessitating millimolar (mM) sample quantities. A breakthrough is presented for utilising Raman spectroscopy in ultrasensitive biomolecular conformation detection, surpassing conventional Raman optical activity by 15 orders of magnitude. This strategy combines chiral plasmonic metasurfaces with achiral molecular Raman reporters and enables the detection of different conformations (α-helix and random coil) of a model peptide (poly-L/D-lysine) at the ≤attomole level (monolayer). This exceptional sensitivity stems from the ability to detect local, molecular-scale changes in the electromagnetic (EM) environment of a chiral nanocavity induced by the presence of biomolecules using molecular Raman reporters. Further signal enhancement is achieved by incorporating achiral Au nanoparticles. The introduction of the nanoparticles creates highly localized regions of extreme optical chirality. This approach, which exploits Raman, a generic phenomenon, paves the way for next-generation technologies for the ultrasensitive detection of diverse biomolecular structures.
- Klíčová slova
- Plasmonics, SERS, chirality, enantiomer, super chirality optical chirality,
- MeSH
- kovové nanočástice chemie MeSH
- molekulární konformace MeSH
- nanotechnologie metody MeSH
- peptidy chemie MeSH
- Ramanova spektroskopie * metody MeSH
- zlato chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- peptidy MeSH
- zlato MeSH
Although several nanomedicines got clinical approval over the past two decades, the clinical translation rate is relatively small so far. There are many post-surveillance withdrawals of nanomedicines caused by various safety issues. For successful clinical advancement of nanotechnology, it is of unmet need to realize cellular and molecular foundation of nanotoxicity. Current data suggest that lysosomal dysfunction caused by nanoparticles is emerging as the most common intracellular trigger of nanotoxicity. This review analyzes prospect mechanisms of lysosomal dysfunction-mediated toxicity induced by nanoparticles. We summarized and critically assessed adverse drug reactions of current clinically approved nanomedicines. Importantly, we show that physicochemical properties have great impact on nanoparticles interaction with cells, excretion route and kinetics, and subsequently on toxicity. We analyzed literature on adverse reactions of current nanomedicines and hypothesized that adverse reactions might be linked with lysosomal dysfunction caused by nanomedicines. Finally, from our analysis it becomes clear that it is unjustifiable to generalize safety and toxicity of nanoparticles, since different particles possess distinct toxicological properties. We propose that the biological mechanism of the disease progression and treatment should be central in the optimization of nanoparticle design.
- Klíčová slova
- Apoptosis, Autophagy, Cancer, Cytotoxicity, Drug-induced liver injury (DILI), Endocytosis, Lysosomes, Nanomedicines, Nanoparticles, Nanotoxicity,
- MeSH
- lidé MeSH
- lyzozomy MeSH
- nanočástice * toxicita chemie MeSH
- nanomedicína * metody MeSH
- nanotechnologie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Many dynamic interactions within the cell microenvironment modulate cell behavior and cell fate. However, the pathways and mechanisms behind cell-cell or cell-extracellular matrix interactions remain understudied, as they occur at a nanoscale level. Recent progress in nanotechnology allows for mimicking of the microenvironment at nanoscale in vitro; electron-beam lithography (EBL) is currently the most promising technique. Although this nanopatterning technique can generate nanostructures of good quality and resolution, it has resulted, thus far, in the production of only simple shapes (e.g., rectangles) over a relatively small area (100 × 100 μm), leaving its potential in biological applications unfulfilled. Here, we used EBL for cell-interaction studies by coating cell-culture-relevant material with electron-conductive indium tin oxide, which formed nanopatterns of complex nanohexagonal structures over a large area (500 × 500 μm). We confirmed the potential of EBL for use in cell-interaction studies by analyzing specific cell responses toward differentially distributed nanohexagons spaced at 1000, 500, and 250 nm. We found that our optimized technique of EBL with HaloTags enabled the investigation of broad changes to a cell-culture-relevant surface and can provide an understanding of cellular signaling mechanisms at a single-molecule level.
- Klíčová slova
- biomimetic surface, cell adhesion and spreading, cell−cell interaction, electron-beam lithography, ligand clustering, nanopatterning, nanospacing,
- MeSH
- buněčná diferenciace MeSH
- buněčné kultury MeSH
- extracelulární matrix MeSH
- nanostruktury * chemie MeSH
- nanotechnologie * metody MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Microfluidics systems can be fabricated in various ways using original silicon glass systems, with easy Si processing and surface modifications for subsequent applications such as cell seeding and their study. Fluorescent imaging of cells became a standard technique for the investigation of cell behavior. Unfortunately, high sensitivity fluorescent imaging, e.g., using total internal reflection fluorescence (TIRF) microscopy, is problematic in these microfluidic systems because the uneven surfaces of the silicon channels' bottoms affect light penetration through the optical filters. In this work, we study the nature of the phenomenon, finding that the problem can be rectified by using a silicon-on-insulator (SOI) substrate, defining the channel depth by the thickness of the top Si layer, and halting the etching at the buried SiO2 layer. Then the fluorescent background signal drops by = 5 times, corresponding to the limit of detection drop from = 0.05 mM to = 50 nM of fluorescein. We demonstrate the importance of a flat surface using TIRF-based single-molecule detection, improving the signal to a noise ratio more than 18 times compared to a conventional Si wafer. Overall, using very high-quality SOI substrates pays off, as it improves the fluorescence image quality due to the increase in signal-to-noise ratio. Concerning the cost of microfluidic device fabrication-design, mask fabrication, wafer processing, and device testing-the initial SOI wafer cost is marginal, and using it improves the system performance.
- MeSH
- křemík * chemie MeSH
- mikrofluidika * MeSH
- nanotechnologie metody MeSH
- oxid křemičitý MeSH
- poměr signál - šum MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- křemík * MeSH
- oxid křemičitý MeSH
Micro/nanomotors are nanoscale devices that have been explored in various fields, such as drug delivery, environmental remediation, or biosensing and diagnosis. The use of micro/nanomotors has grown considerably over the past few years, partially because of the advantages that they offer in the development of new conceptual avenues in biosensing. This is due to their propulsion and intermixing in solution compared with their respective static forms, which enables motion-based detection methods and/or decreases bioassay time. This review focuses on the impacts of micro/nanomotors on biosensing research in the last 2 years. An overview of designs for bioreceptor attachment to micro/nanomotors is given. Recent developments have focused on chemically propelled micromotors using external fuels, commonly hydrogen peroxide. However, the associated fuel toxicity and inconvenience of use in relevant biological samples such as blood have prompted researchers to explore new micro/nanomotor biosensing approaches based on biocompatible propulsion sources such as magnetic or ultrasound fields. The main advances in biocompatible propulsion sources for micro/nanomotors as novel biosensing platforms are discussed and grouped by their propulsion-driven forces. The relevant analytical applications are discussed and representatively illustrated. Moreover, envisioning future biosensing applications, the principal advantages of micro/nanomotor synthesis using biocompatible and biodegradable materials are given. The review concludes with a realistic drawing on the present and future perspectives.
- Klíčová slova
- Biofluid, Biomedical analysis, Biosensing, Micromotors, Propulsion,
- MeSH
- lékové transportní systémy MeSH
- nanostruktury * MeSH
- nanotechnologie metody MeSH
- peroxid vodíku MeSH
- regenerace a remediace životního prostředí * MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- peroxid vodíku MeSH
In the last decade, significant advances have been made towards the rational design of proteins, DNA, and other organic nanostructures. The emerging possibility to precisely engineer molecular structures resulted in a wide range of new applications in fields such as biotechnology or medicine. The complexity and size of the artificial molecular systems as well as the number of interactions are greatly increasing and are manifesting the need for computational design support. In addition, a new generation of AI-based structure prediction tools provides researchers with completely new possibilities to generate recombinant proteins and functionalized DNA nanostructures. In this study, we present Catana, a web-based modelling environment suited for proteins and DNA nanostructures. User-friendly features were developed to create and modify recombinant fusion proteins, predict protein structures based on the amino acid sequence, and manipulate DNA origami structures. Moreover, Catana was jointly developed with the novel Unified Nanotechnology Format (UNF). Therefore, it employs a state-of-the-art coarse-grained data model, that is compatible with other established and upcoming applications. A particular focus was put on an effortless data export to allow even inexperienced users to perform in silico evaluations of their designs by means of molecular dynamics simulations. Catana is freely available at http://catana.ait.ac.at/.
- MeSH
- DNA chemie MeSH
- konformace nukleové kyseliny MeSH
- nanostruktury * chemie MeSH
- nanotechnologie metody MeSH
- nukleové kyseliny * MeSH
- rekombinantní fúzní proteiny MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DNA MeSH
- nukleové kyseliny * MeSH
- rekombinantní fúzní proteiny MeSH
DNA nanotechnology has yielded remarkable advances in composite materials with diverse applications in biomedicine. The specificity and predictability of building 3D structures at the nanometer scale make DNA nanotechnology a promising tool for uses in biosensing, drug delivery, cell modulation, and bioimaging. However, for successful translation of DNA nanostructures to real-world applications, it is crucial to understand how they interact with living cells, and the consequences of such interactions. In this review, we summarize the current state of knowledge on the interactions of DNA nanostructures with cells. We identify key challenges, from a cell biology perspective, that influence progress towards the clinical translation of DNA nanostructures. We close by providing an outlook on what questions must be addressed to accelerate the clinical translation of DNA nanostructures. STATEMENT OF SIGNIFICANCE: Self-assembled DNA nanostructures (DNs) offers unique opportunities to overcome persistent challenges in the nanobiotechnology field. However, the interactions between engineered DNs and living cells are still not well defined. Critical systematization of current cellular models and biological responses triggered by DNs is a crucial foundation for the successful clinical translation of DNA nanostructures. Moreover, such an analysis will identify the pitfalls and challenges that are present in the field, and provide a basis for overcoming those challenges.
- Klíčová slova
- Bionano interactions, Cellular uptake, Cytotoxicity, DNA nanotechnology, Nanotechnology, Protein corona,
- MeSH
- DNA chemie MeSH
- lékové transportní systémy metody MeSH
- nanostruktury * chemie MeSH
- nanotechnologie metody MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- DNA MeSH
MicroRNAs (miRNA) are key regulators of gene expression, controlling different biological processes such as cellular development, differentiation, proliferation, metabolism, and apoptosis. The relationships between miRNA expression and the onset and progression of different diseases, such as tumours, cardiovascular and rheumatic diseases, and neurological disorders, are well known. A nanotechnology-based approach could match miRNA delivery and detection to move beyond the proof-of-concept stage. Different kinds of nanotechnologies can have a major impact on the diagnosis and treatment of miRNA-related diseases such as cancer. Developing novel methodologies aimed at clinical practice represents a big challenge for the early diagnosis of specific diseases. Within this context, nanotechnology represents a wide emerging area at the forefront of research over the last two decades, whose potential has yet to be fully attained. Nanomedicine, derived from nanotechnology, can exploit the unique properties of nanometer-sized particles for diagnostic and therapeutic purposes. Through nanomedicine, specific treatment to counteract only cancer-cell proliferation will be improved, while leaving healthy cells intact. In this review, we dissect the properties of different nanocarriers and their roles in the early detection and treatment of cancer.
- Klíčová slova
- nanotechnology biomarker, nano–microRNA, target therapy,
- MeSH
- lidé MeSH
- mikro RNA * metabolismus MeSH
- nádory * diagnóza genetika terapie MeSH
- nanomedicína MeSH
- nanotechnologie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- mikro RNA * MeSH