Correlated cell migration in fibrous extracellular matrix (ECM) is important in many biological processes. During migration, cells can remodel the ECM, leading to the formation of mesoscale structures such as fiber bundles. However,h ow such mesoscale structures regulate correlated single-cells migration remains to be elucidated. Here,u sing aq uasi-3D in vitro model, we investigate how collagen fiber bundles are dynamically re-organized and guide cell migration. By combining laser ablation technique with 3D tracking and active-particle simulations,w ed efinitively showt hat only the re-organized fiber bundles that carry significant tensile forces can guide strongly correlated cell migration, providing for the first time adirect experimental evidence supporting that matrix-transmitted long-range forces can regulate cell migration and self-organization. This force regulation mechanism can providen ew insights for studies on cellular dynamics, fabrication or selection of biomedical materials in tissue repairing, and many other biomedical applications.
As a novel X-ray focusing technology, lobster-eye micropore optics (MPO) feature both a wide observing field of view and true imaging capability, promising sky monitoring with significantly improved sensitivity and spatial resolution in soft X-rays. Since first proposed by Angel, the optics have been extensively studied, developed and trialed over the past decades. In this Letter, we report on the first-light results from a flight experiment of the Lobster Eye Imager for Astronomy, a pathfinder of the wide-field X-ray telescope of the Einstein Probe mission. The piggyback imager, launched in 2022 July, has a mostly unvignetted field of view of 18.°6 × 18.°6. Its spatial resolution is in the range of 4′–7′ in FWHM and the focal spot effective area is 2–3 cm2, both showing only mild fluctuations across the field of view. We present images of the Galactic center region, Sco X-1, and the diffuse Cygnus Loop nebular taken in snapshot observations over 0.5–4 keV. These are truly wide-field X-ray images of celestial bodies observed, for the first time, by a focusing imaging telescope. Initial analyses of the in-flight data show excellent agreement between the observed images and the on-ground calibration and simulations. The instrument and its characterization are briefly described, as well as the flight experiment. The results provide a solid basis for the development of the present and proposed wide-field X-ray missions using lobster-eye MPO.
SARS-CoV-2 has caused a severe pneumonia pandemic worldwide with high morbidity and mortality. How to develop a preclinical model for recapitulating SARS-CoV-2 pathogenesis is still urgent and essential for the control of the pandemic. Here, we have established a 3D biomimetic alveolus-on-a-chip with mechanical strain and extracellular matrix taken into consideration. We have validated that the alveolus-on-a-chip is capable of recapitulating key physiological characteristics of human alveolar units, which lays a fundamental basis for viral infection studies at the organ level. Using virus-analogous chemicals and pseudovirus, we have explored virus pathogenesis and blocking ability of antibodies during viral infection. This work provides a favorable platform for SARS-CoV-2-related researches and has a great potential for physiology and pathophysiology studies of the human lung at the organ level in vitro.
It is a big challenge to measure position changes of biomolecules in the direction normal to the plasma membranes of living cells. We developed a one donor-multiple quenchers Fӧrster resonance energy transfer method by using non-fluorescent quenchers in the extracellular environment. It senses subnanometer position changes of a fluorophore-labeled biomolecule in the plasma membrane. The method was validated by monitoring flip-flops of individual lipid molecules incorporated in plasma membranes. We studies membrane perforation by a host defense peptide from the extracellular side and found that the pore-forming peptide is dynamic, switching among different insertion depths. The method is especially useful in studying interactions of membrane proteins with the inner surfaces of plasma membranes. Our method will find wide applications in systematic analysis of fundamental cellular processes at plasma membranes.
While two-dimensional infrared (2D-IR) spectroscopy is uniquely suitable for monitoring femtosecond (fs) to picosecond (ps) water dynamics around static protein structures, its utility for probing enzyme active-site dynamics is limited due to the lack of site-specific 2D-IR probes. We demonstrate the genetic incorporation of a novel 2D-IR probe, m-azido-l-tyrosine (N3Y) in the active-site of DddK, an irondependent enzyme that catalyzes the conversion of dimethylsulfoniopropionate to dimethylsulphide. Our results show that both the oxidation of active-site iron to Fe III , and the addition of denaturation reagents, result in significant decrease in enzyme activity and active-site water motion confinement. As tyrosine residues play important roles, including as general acids and bases, and electron transfer agents in many key enzymes, the genetically encoded 2D-IR probe N3Y should be broadly applicable to investigate how the enzyme active-site motions at the fs-ps time scale direct reaction pathways to facilitating specific chemical reactions.
Constructing proper in vitro tumor immune microenvironment (TIME) is important for cancer immune‐therapy studies, while the selection of biomaterials is critical. As innate immune cells, macrophages can target and kill cancer cells in vivo at the early stage of tumor development. However, this targeting phenomenon has not been observed in vitro. Herein, a quasi‐3D in vitro cell culture model is constructed to mimic TIME by integrating hydrogel collagen as extracellular matrix for cells. In the collagen‐based quasi‐3D in vitro system, for the first time, it is found that macrophages can be attracted toward cancer cells along the dynamically reconstructed collagen fibers. By combining traction force microscopy and customized micro‐manipulator system, it is revealed that the collagen matrix‐transmitted tensile force signaling precisely guides the migration of macrophages toward cancer cells. The mechano‐responsiveness mechanism is related to the activation of mechanosensitive ion channels, and the induced local increase of calcium signal, which is proved to enhance the F‐actin assembly and to guide the cell migration. This novel mechanism advances the understanding of the role of collagen fibers in mechanotaxis of macrophages. Taken together, it has great potential for assisting biomaterial designs in developing new drug‐screening models and clinical strategies for cancer immune‐therapy.
Fibrous Proteins In their Research Article on page 11858, Yuanjin Zhao, Yang Jiao, Fangfu Ye et al. report the organization of collagen fiber bundles. The bundles transmit mechanical signals and induce strongly correlated cell migration.
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