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We demonstrate self-sensing tungsten disulfide nanotube (WS2 NT) torsional resonators. These resonators exhibit all-electrical self-sensing operation with electrostatic excitation and piezoresistive motion detection. We show that the torsional motion of the WS2 NT resonators results in a change of the nanotube electrical resistance, with the most significant change around their mechanical resonance, where the amplitude of torsional vibrations is maximal. Atomic force microscopy analysis revealed the torsional and bending stiffness of the WS2 NTs, which we used for modeling the behavior of the WS2 NT devices. In addition, the solution of the electrostatic boundary value problem shows how the spatial potential and electrostatic field lines around the device impact its capacitance. The results uncover the coupling between the electrical and mechanical behaviors of WS2 and emphasize their potential to operate as key components in functional devices, such as nanosensors and radio frequency devices.
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T cells sense both chemical cues delivered by antigen molecules and physical cues delivered by the environmental elasticity and topography; yet, it is still largely unclear how these cues cumulatively regulate the immune activity of T cells. Here, we engineered a nanoscale platform for ex vivo stimulation of T cells based on antigen-functionalized nanowires. The nanowire topography and elasticity, as well as the immobilized antigens, deliver the physical and chemical cues, respectively, enabling the systematic study of the integrated effect of these cues on a T cell's immune response. We found that T cells sense both the topography and bending modulus of the nanowires and modulate their signaling, degranulation, and cytotoxicity with the variation in these physical features. Our study provides an important insight into the physical mechanism of T cell activation and paves the way to novel nanomaterials for the controlled ex vivo activation of T cells in immunotherapy.
Assuntos
Nanofios , Anticorpos , Antígenos , Imunoterapia , Linfócitos TRESUMO
The cytotoxic activity of natural killer (NK) cells is regulated by many chemical and physical cues, whose integration mechanism is still obscure. Here, a multifunctional platform is engineered for NK cell stimulation, to study the effect of the signal integration and spatial heterogeneity on NK cell function. The platform is based on nanowires, whose mechanical compliance and site-selective tip functionalization with antigens produce the physical and chemical stimuli, respectively. The nanowires are confined to micron-sized islands, which induce a splitting of the NK cells into two subpopulations with distinct morphologies and immune responses: NK cells atop the nanowire islands display symmetrical spreading and enhanced activation, whereas cells lying in the straits between the islands develop elongated profiles and show lower activation levels. The demonstrated tunability of NK cell cytotoxicity provides an important insight into the mechanism of their immune function and introduces a novel technological route for the ex vivo shaping of cytotoxic lymphocytes in immunotherapy.
Assuntos
Antineoplásicos , Nanofios , Antígenos , Citotoxicidade Imunológica , Imunoterapia , Células Matadoras NaturaisRESUMO
Phase Change Materials (PCMs) have demonstrated tremendous potential as a platform for achieving diverse functionalities in active and reconfigurable micro-nanophotonic devices across the electromagnetic spectrum, ranging from terahertz to visible frequencies. This comprehensive roadmap reviews the material and device aspects of PCMs, and their diverse applications in active and reconfigurable micro-nanophotonic devices across the electromagnetic spectrum. It discusses various device configurations and optimization techniques, including deep learning-based metasurface design. The integration of PCMs with Photonic Integrated Circuits and advanced electric-driven PCMs are explored. PCMs hold great promise for multifunctional device development, including applications in non-volatile memory, optical data storage, photonics, energy harvesting, biomedical technology, neuromorphic computing, thermal management, and flexible electronics.
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[This corrects the article DOI: 10.1016/j.isci.2023.107946.].
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The role of juxtaposition of activating and inhibitory receptors in signal inhibition of cytotoxic lymphocytes remains strongly debated. The challenge lies in the lack of tools that allow simultaneous spatial manipulation of signaling molecules. To circumvent this, we produced a nanoengineered multifunctional platform with molecular-scale spatial control of ligands, which was applied to elucidate KIR2DL1-mediated inhibition of NKG2D signaling-receptors of natural killer cells. This platform was conceived by bimetallic nanodot patterning with molecular-scale registry, followed by a ternary functionalization with distinct moieties. We found that a 40-nm gap between activating and inhibitory ligands provided optimal inhibitory conditions. Supported by theoretical modeling, we interpret these findings as a consequence of the size mismatch and conformational flexibility of ligands in their spatial interaction. This highly versatile approach provides an important insight into the spatial mechanism of inhibitory immune checkpoints, which is essential for the rational design of future immunotherapies.
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Controlled assembly of nanostructures is a key challenge in nanotechnology. In this work, we introduce an approach for the controlled assembly of 1D nanodumbbells-Au-tipped semiconductor nanorods-into arbitrary 2D higher architectures, by their chemical docking to nanopatterned functionalities. We realized the docking functionalities via nanoimprinted metallic nanodots functionalized with an organic monolayer, whose terminal thiol groups chemically bind the nanodumbbell tips. We demonstrated that the functional nanopattern encodes the nanodumbbell assembly and can be designed to deterministically position nanodumbbells in two possible modes. In the single-docking mode, the nanodot arrays are designed with a spacing that exceeds the nanodumbbell length, restricting each nanodumbbell to dock with one edge and physically connect with its free edge to one of the neighboring nanodumbbells. Alternatively, in the double-docking mode, the nanodots are spaced to exactly fit the nanodumbbell length, allowing nanodumbbell docking with both edges. We found that the docking kinetics can be described by a random attachment model, and verified that for the used docking chemistry, nanodumbbells that are docked to the same dot do not interact with each other. Our work demonstrates the possibility for massively parallel positioning of sub-100 nm 1D semiconductor nanostructures, and can potentially enable their future integration into functional nanodevices and nanosystems.
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NK cells recognize cancer and viral cells by binding their activating receptors to antigens presenting on the membrane of target cells. Although the activation mechanism of NK cells is a subject of extensive research today, the role of the composition and spatial distribution of activating ligands in NK cell cytotoxicity is barely understood. In this work, we engineered a nanochip whose surface was patterned with matrices of antigens for NKG2D activating receptors. These matrices mimicked the spatial order of the surface of antigen presenting cells with molecular resolution. Using this chip, we elucidated the effect of the antigen spatial distribution on the NK cell spreading and immune activation. We found that the spatial distribution of the ligand within the 100 nm length-scale provides the minimal conditions for NKG2D regulated cell spreading. Furthermore, we found that the immune activation of NK cells requires the same minimal spatial distribution of activating ligands. Above this threshold, both spreading and activation plateaued, confirming that these two cell functions work hand in hand. Our study provides an important insight on the spatial mechanism of the cytotoxic activity of NK cells. This insight opens the way to rationally designed antitumor therapies that harness NK cytotoxicity.