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1. Self-organizing behaviors of cardiovascular cells on synthetic nanofiber scaffolds

   https://doi.org/10.1063/5.0172423  

   Peters, Michael_M; Brister, Jackson_K; Tang, Edward_M; Zhang, Felita_W; Lucian, Veronica_M; Trackey, Paul_D; Bone, Zachary; Zimmerman, John_F; Jin, Qianru; Burpo, F_John; et al (December 2023, APL Bioengineering)

   In tissues and organs, the extracellular matrix (ECM) helps maintain inter- and intracellular architectures that sustain the structure–function relationships defining physiological homeostasis. Combining fiber scaffolds and cells to form engineered tissues is a means of replicating these relationships. Engineered tissues' fiber scaffolds are designed to mimic the topology and chemical composition of the ECM network. Here, we asked how cells found in the heart compare in their propensity to align their cytoskeleton and self-organize in response to topological cues in fibrous scaffolds. We studied cardiomyocytes, valvular interstitial cells, and vascular endothelial cells as they adapted their inter- and intracellular architectures to the extracellular space. We used focused rotary jet spinning to manufacture aligned fibrous scaffolds to mimic the length scale and three-dimensional (3D) nature of the native ECM in the muscular, valvular, and vascular tissues of the heart. The representative cardiovascular cell types were seeded onto fiber scaffolds and infiltrated the fibrous network. We measured different cell types' propensity for cytoskeletal alignment in response to fiber scaffolds with differing levels of anisotropy. The results indicated that valvular interstitial cells on moderately anisotropic substrates have a higher propensity for cytoskeletal alignment than cardiomyocytes and vascular endothelial cells. However, all cell types displayed similar levels of alignment on more extreme (isotropic and highly anisotropic) fiber scaffold organizations. These data suggest that in the hierarchy of signals that dictate the spatiotemporal organization of a tissue, geometric cues within the ECM and cellular networks may homogenize behaviors across cell populations and demographics. 

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2. Laser induced graphene-based glucose biofuel cell

   https://doi.org/10.1109/SENSORS47087.2021.9639554  

   Hossain, Md Faruk; Slaughter, Gymama (October 2021, 2021 IEEE Sensors)

   A glucose biofuel cell is presented using laser induced 3D graphene (LIG) substrate integrated with catalytic active nanomaterials for harnessing the biochemical energy of glucose. The LIG anode comprised glucose dehydrogenase immobilized on reduced graphene oxide and multiwalled carbon nanotubes (RGO/MWCNTs) nanocomposite for glucose oxidation. The LIG cathode is modified with RGO/MWCNTs and silver oxide (Ag 2 O) nanocomposites for the reduction of oxygen. The assembled biofuel cell exhibited a linear peak power response up to 18 mM glucose with sensitivity of 0.63 μW mM -1 cm −2 and exhibited good linearity (r 2 = 0.99). The glucose biofuel cell showed an open-circuit voltage of 0.365 V, a maximum power density of 11.3 μW cm −2 at a cell voltage of 0.25 V, and a short-circuit current density of 45.18 μA cm −2 when operating in 18 mM glucose. Cyclic voltammetry revealed the bioanode exhibited similar linearity for the detection of glucose. These results demonstrate that LIG based bioelectrodes offer great promise for diverse applications in the development of hybrid biofuel cell and biosensor technology. 

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3. The LINC complex is required for endothelial cell adhesion and adaptation to shear stress and cyclic stretch

   https://doi.org/10.1091/mbc.E20-11-0698  

   Denis, Kevin B.; Cabe, Jolene I.; Danielsson, Brooke E.; Tieu, Katie V.; Mayer, Carl R.; Conway, Daniel E. (August 2021, Molecular Biology of the Cell)

   Discher, Dennis (Ed.)

   The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex is a structure consisting of nesprin, SUN, and lamin proteins. A principal function of the LINC complex is anchoring the nucleus to the actin, microtubule, and intermediate filament cytoskeletons. The LINC complex is present in nearly all cell types, including endothelial cells. Endothelial cells line the innermost surfaces of blood vessels and are critical for blood vessel barrier function. In addition, endothelial cells have specialized functions, including adaptation to the mechanical forces of blood flow. Previous studies have shown that depletion of individual nesprin isoforms results in impaired endothelial cell function. To further investigate the role of the LINC complex in endothelial cells we utilized dominant negative KASH (DN-KASH), a dominant negative protein that displaces endogenous nesprins from the nuclear envelope and disrupts nuclear–cytoskeletal connections. Endothelial cells expressing DN-KASH had altered cell–cell adhesion and barrier function, as well as altered cell–matrix adhesion and focal adhesion dynamics. In addition, cells expressing DN-KASH failed to properly adapt to shear stress or cyclic stretch. DN-KASH–expressing cells exhibited impaired collective cell migration in wound healing and angiogenesis assays. Our results demonstrate the importance of an intact LINC complex in endothelial cell function and homeostasis. 

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4. Emerging investigator series: a multispecies analysis of the relationship between oxygen content and toxicity in graphene oxide

   https://doi.org/10.1039/d0en01264e  

   Barrios, Ana C.; Cahue, Yaritza P.; Wang, Yan; Geiger, Jason; Puerari, Rodrigo C.; Matias, William Gerson; Melegari, Silvia Pedroso; Gilbertson, Leanne M.; Perreault, François (June 2021, Environmental Science: Nano)

   null (Ed.)

   The toxicity of graphene oxide (GO) has been documented for multiple species. However, GO has variable surface chemistry, and it is currently unclear whether changes in oxygen content impact GO-organism interactions the same way across species. In this study, a modified Hummer's GO (ARGO) was systematically reduced by thermal annealing at 200, 500, or 800 °C and toxicity towards bacteria ( Escherichia coli ), alga ( Scenedesmus obliquus ), cyanobacteria ( Microcystis aeruginosa ), and invertebrates ( Daphnia magna ) was assessed by measuring the effective concentrations inducing 50% inhibition (EC 50 ). The EC 50 –carbon/oxygen ratio relationships show similar trends for bacteria and invertebrates, where toxicity increases as the material is reduced. Conversely, cyanobacterial inhibition decreases as GO is reduced. Further testing supports differences in cell-GO interactions between bacteria and cyanobacteria. Cyanobacteria showed a decrease in metabolic activity, evidenced by a 69% reduction in esterase activity after ARGO exposure but no oxidative stress, measured by 2′,7′-dichlorodihydrofluorescein diacetate (H 2 DCFDA) fluorescence and catalase activity. In contrast, ARGO induced a 55% increase in H 2 DCFDA fluorescence and 342% increase in catalase activity in bacteria. These changes in cell–material interactions propose different mechanisms of action, a physical mechanism occurring in cyanobacteria, and a chemical mechanism in bacteria. The differences in GO toxicity observed in different organisms emphasize the need to differentiate the safe-by-design guidelines made for GO in relation to the potential organisms exposed. 

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5. Junctions at the crossroads: the impact of mechanical cues on endothelial cell-cell junction conformations and vascular permeability

   https://doi.org/10.1152/ajpcell.00605.2023  

   Brandon, Ken D; Frank, William E; Stroka, Kimberly M (October 2024, American Journal of Physiology-Cell Physiology)

   Cells depend on precisely regulating barrier function within the vasculature to maintain physiological stability and facilitate essential substance transport. Endothelial cells achieve this through specialized adherens and tight junction protein complexes, which govern paracellular permeability across vascular beds. Adherens junctions, anchored by vascular endothelial (VE)-cadherin and associated catenins to the actin cytoskeleton, mediate homophilic adhesion crucial for barrier integrity. In contrast, tight junctions composed of occludin, claudin, and junctional adhesion molecule A interact with Zonula Occludens proteins, reinforcing intercellular connections essential for barrier selectivity. Endothelial cell-cell junctions exhibit dynamic conformations during development, maturation, and remodeling, regulated by local biochemical and mechanical cues. These structural adaptations play pivotal roles in disease contexts such as chronic inflammation, where junctional remodeling contributes to increased vascular permeability observed in conditions from cancer to cardiovascular diseases. Conversely, the brain microvasculature’s specialized junctional arrangements pose challenges for therapeutic drug delivery due to their unique molecular compositions and tight organization. This commentary explores the molecular mechanisms underlying endothelial cell-cell junction conformations and their implications for vascular permeability. By highlighting recent advances in quantifying junctional changes and understanding mechanotransduction pathways, we elucidate how physical forces from cellular contacts and hemodynamic flow influence junctional dynamics. 

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