Tissue-Engineered Microvessels: A Review of Current Engineering Strategies and Applications.

Microvessels, including arterioles, capillaries, and venules, play an important role in regulating blood flow, enabling nutrient and waste exchange, and facilitating immune surveillance. Due to their important roles in maintaining normal function in human tissues, a substantial effort has been devoted to developing tissue-engineered models to study endothelium-related biology and pathology. Various engineering strategies have been developed to recapitulate the structural, cellular, and molecular hallmarks of native human microvessels in vitro.

Long noncoding RNA MALAT1 is dynamically regulated in leader cells during collective cancer invasion.

Cancer cells collectively invade using a leader-follower organization, but the regulation of leader cells during this dynamic process is poorly understood. Using a dual double-stranded locked nucleic acid (LNA) nanobiosensor that tracks long noncoding RNA (lncRNA) dynamics in live single cells, we monitored the spatiotemporal distribution of lncRNA during collective cancer invasion. We show that the lncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is dynamically regulated in the invading fronts of cancer cells and patient-derived spheroids.

A sticky-end probe biosensor for homogeneous detection of transcription factor binding activity.

Transcription factors are essential regulators of various physiological and pathological processes. However, detecting transcription factor-DNA binding activities is often time-consuming and labor-intensive. Homogeneous biosensors that are compatible with mix-and-measure protocols have the potential to simplify the workflow for therapeutic screening and disease diagnostics.

Transient nuclear deformation primes epigenetic state and promotes cell reprogramming.

Cell reprogramming has wide applications in tissue regeneration, disease modelling and personalized medicine. In addition to biochemical cues, mechanical forces also contribute to the modulation of the epigenetic state and a variety of cell functions through distinct mechanisms that are not fully understood. Here we show that millisecond deformation of the cell nucleus caused by confinement into microfluidic channels results in wrinkling and transient disassembly of the nuclear lamina, local detachment of lamina-associated domains in chromatin and a decrease of histone methylation (histone H3 lysine 9 trimethylation) and DNA methylation.

Nrf2 Modulates the Hybrid Epithelial/Mesenchymal Phenotype and Notch Signaling During Collective Cancer Migration.

Hybrid epithelial/mesenchymal cells (E/M) are key players in aggressive cancer metastasis. It remains a challenge to understand how these cell states, which are mostly non-existent in healthy tissue, become stable phenotypes participating in collective cancer migration. The transcription factor Nrf2, which is associated with tumor progression and resistance to therapy, appears to be central to this process.

Optimizing locked nucleic acid modification in double-stranded biosensors for live single cell analysis.

Double-stranded (ds) biosensors are homogeneous oligonucleotide probes for detection of nucleic acid sequences in biochemical assays and live cell imaging. Locked nucleic acid (LNA) modification can be incorporated in the biosensors to enhance the binding affinity, specificity, and resistance to nuclease degradation. However, LNA monomers in the quencher sequence can also prevent the target-fluorophore probe binding, which reduces the signal of the dsLNA biosensor.

A transparent low intensity pulsed ultrasound (LIPUS) chip for high-throughput cell stimulation.

We report an on-chip platform for low-intensity pulsed ultrasound (LIPUS) stimulation of cells directly cultured on a biocompatible surface of a transparent ultrasound transducer (TUT) fabricated using lithium niobate. The high light transmittance (>80%) and compact size (3 mm × 3 mm × 2 mm) of TUTs allowed easy integration with powerful optical microscopy techniques with no additional acoustic coupling and risk for contamination. TUTs were excited with varying acoustic excitation parameters (voltage amplitude and duty cycle) and resulting live cell calcium signaling was simultaneously imaged using time-lapse confocal microscopy, while the temperature change was measured by a thermocouple.

Advances in Viral Diagnostic Technologies for Combating COVID-19 and Future Pandemics.

The emergence of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens the health of the global population and challenges our preparedness for pandemic threats. Previous outbreaks of coronaviruses and other viruses have suggested the importance of diagnostic technologies in fighting viral outbreaks. Nucleic acid detection techniques are the gold standard for detecting SARS-CoV-2.

DNA Transformer for Visualizing Endogenous RNA Dynamics in Live Cells.

The functions of RNA are tightly regulated via diverse intracellular mechanisms. However, probing the complex dynamics of endogenous RNA in live cells is a challenging task. In the present study, a DNA transformer is designed for visualizing the abundance, distribution, and mobility of endogenous mRNAs in live human cells.

Nanowire Magnetoscope Reveals a Cellular Torque with Left-Right Bias.

Cellular force regulates many types of cell mechanics and the associated physiological behaviors. Recent evidence suggested that cell motion with left-right (LR) bias may be the origin of LR asymmetry in tissue architecture. As actomyosin activity was found essential in the process, it predicts a type of cellular force that coordinates the development of LR asymmetry in tissue formation.

Substrate Stiffness Regulates the Development of Left-Right Asymmetry in Cell Orientation.

Left-right (LR) asymmetry of tissue/organ structure is a morphological feature essential for many tissue functions. The ability to incorporate the LR formation in constructing tissue/organ replacement is important for recapturing the inherent tissue structure and functions. However, how LR asymmetry is formed remains largely underdetermined, which creates significant hurdles to reproduce and regulate the formation of LR asymmetry in an engineering context.