Tumor Biomechanics Alters Metastatic Dissemination of Triple Negative Breast Cancer via Rewiring Fatty Acid Metabolism.

In recent decades, the role of tumor biomechanics on cancer cell behavior at the primary site has been increasingly appreciated. However, the effect of primary tumor biomechanics on the latter stages of the metastatic cascade, such as metastatic seeding of secondary sites and outgrowth remains underappreciated. This work sought to address this in the context of triple negative breast cancer (TNBC), a cancer type known to aggressively disseminate at all stages of disease progression. Using mechanically tuneable model systems, mimicking the range of stiffness's typically found within breast tumors, it is found that, contrary to expectations, cancer cells exposed to softer microenvironments are more able to colonize secondary tissues. It is shown that heightened cell survival is driven by enhanced metabolism of fatty acids within TNBC cells exposed to softer microenvironments. It is demonstrated that uncoupling cellular mechanosensing through integrin ß1 blocking antibody effectively causes stiff primed TNBC cells to behave like their soft counterparts, both in vitro and in vivo. This work is the first to show that softer tumor microenvironments may be contributing to changes in disease outcome by imprinting on TNBC cells a greater metabolic flexibility and conferring discrete cell survival advantages.

Timothy Grass Pollen Induces Spatial Reorganisation of F-Actin and Loss of Junctional Integrity in Respiratory Cells.

Grass pollens have been identified as mediators of respiratory distress, capable of exacerbating respiratory diseases including epidemic thunderstorm asthma (ETSA). It is hypothesised that during thunderstorms, grass pollen grains swell to absorb atmospheric water, rupture, and release internal protein content to the atmosphere. The inhalation of atmospheric grass pollen proteins results in deadly ETSA events. We sought to identify the underlying cellular mechanisms that may contribute towards the severity of ETSA in temperate climates using Timothy grass (Phleum pratense). Respiratory cells exposed to Timothy grass pollen protein extract (PPE) caused cells to undergo hypoxia ultimately triggering the subcellular re-organisation of F-actin from the peri junctional belt to cytoplasmic fibre assembly traversing the cell body. This change in actin configuration coincided with the spatial reorganisation of microtubules and importantly, decreased cell compressibility specifically at the cell centre. Further to this, we find that the pollen-induced reorganisation of the actin cytoskeleton prompting secretion of the pro-inflammatory cytokine, interleukin-8. In addition, the loss of peri-junctional actin following exposure to pollen proteins was accompanied by the release of epithelial transmembrane protein, E-cadherin from cell-cell junctions resulting in a decrease in epithelial barrier integrity. We demonstrate that Timothy grass pollen regulates F-actin dynamics and E-cadherin localisation in respiratory cells to mediate cell-cell junctional integrity highlighting a possible molecular pathway underpinning ETSA events.

Synthesis of Ge1-xSnx Alloy Thin Films by Rapid Thermal Annealing of Sputtered Ge/Sn/Ge Layers on Si Substrates.

In this work, nanocrystalline Ge1-xSnx alloy formation from a rapid thermal annealed Ge/Sn/Ge multilayer has been presented. The multilayer was magnetron sputtered onto the Silicon substrate. This was followed by annealing the layers by rapid thermal annealing, at temperatures of 300 °C, 350 °C, 400 °C, and 450 °C, for 10 s. Then, the effect of thermal annealing on the morphological, structural, and optical characteristics of the synthesized Ge1-xSnx alloys were investigated. The nanocrystalline Ge1-xSnx formation was revealed by high-resolution X-ray diffraction (HR-XRD) measurements, which showed the orientation of (111). Raman results showed that phonon intensities of the Ge-Ge vibrations were improved with an increase in the annealing temperature. The results evidently showed that raising the annealing temperature led to improvements in the crystalline quality of the layers. It was demonstrated that Ge-Sn solid-phase mixing had occurred at a low temperature of 400 °C, which led to the creation of a Ge1-xSnx alloy. In addition, spectral photo-responsivity of a fabricated Ge1-xSnx metal-semiconductor-metal (MSM) photodetector exhibited its extending wavelength into the near-infrared region (820 nm).