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1. Endothelial glycocalyx sensitivity to chemical and mechanical sub-endothelial substrate properties

   https://doi.org/10.3389/fbioe.2023.1250348  

   Hamrangsekachaee, Mohammad; Wen, Ke; Yazdani, Narges; Willits, Rebecca K; Bencherif, Sidi A; Ebong, Eno E (October 2023, Frontiers in Bioengineering and Biotechnology)

   Glycocalyx (GCX) is a carbohydrate-rich structure that coats the surface of endothelial cells (ECs) and lines the blood vessel lumen. Mechanical perturbations in the vascular environment, such as blood vessel stiffness, can be transduced and sent to ECs through mechanosensors such as GCX. Adverse stiffness alters GCX-mediated mechanotransduction and leads to EC dysfunction and eventually atherosclerotic cardiovascular diseases. To understand GCX-regulated mechanotransduction events, anin vitromodel emulatingin vivovessel conditions is needed. To this end, we investigated the impact of matrix chemical and mechanical properties on GCX expression via fabricating a tunable non-swelling matrix based on the collagen-derived polypeptide, gelatin. To study the effect of matrix composition, we conducted a comparative analysis of GCX expression using different concentrations (60–25,000 μg/mL) of gelatin and gelatin methacrylate (GelMA) in comparison to fibronectin (60 μg/mL), a standard coating material for GCX-related studies. Using immunocytochemistry analysis, we showed for the first time that different substrate compositions and concentrations altered the overall GCX expression on human umbilical vein ECs (HUVECs). Subsequently, GelMA hydrogels were fabricated with stiffnesses of 2.5 and 5 kPa, representing healthy vessel tissues, and 10 kPa, corresponding to diseased vessel tissues. Immunocytochemistry analysis showed that on hydrogels with different levels of stiffness, the GCX expression in HUVECs remained unchanged, while its major polysaccharide components exhibited dysregulation in distinct patterns. For example, there was a significant decrease in heparan sulfate expression on pathological substrates (10 kPa), while sialic acid expression increased with increased matrix stiffness. This study suggests the specific mechanisms through which GCX may influence ECs in modulating barrier function, immune cell adhesion, and mechanotransduction function under distinct chemical and mechanical conditions of both healthy and diseased substrates. 

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2. Modeling the blood–brain barrier: Beyond the endothelial cells

   https://doi.org/10.1016/j.cobme.2017.11.002  

   Gastfriend, Benjamin D.; Palecek, Sean P.; Shusta, Eric V. (March 2018, Current Opinion in Biomedical Engineering)
3. The role of shear stress and altered tissue properties on endothelial to mesenchymal transformation and tumor-endothelial cell interaction

   https://doi.org/10.1063/1.4991738  

   Mina, Sara G.; Huang, Peter; Murray, Bruce T.; Mahler, Gretchen J. (July 2017, Biomicrofluidics)
4. Lack of Laminar Shear Stress Facilitates the Endothelial Uptake of Very Small Superparamagnetic Iron Oxide Nanoparticles by Modulating the Endothelial Surface Layer

   https://doi.org/10.2147/IJN.S437714  

   Twamley, Shailey; Gimber, Niclas; Sánchez-Ibarra, Héctor; Christaller, Tobias; Isakzai, Victoria; Kratz, Harald; Mitra, Ronodeep; Kampen, Lena; Stach, Anke; Heilmann, Heike; et al (January 2024, International Journal of Nanomedicine)
5. As the endothelial cell reorients, its tensile forces stabilize

   https://doi.org/https://doi.org/10.1016/j.jbiomech.2020.109770  

   Stamenovic, D; Krishnan, R; Smith, ML (May 2020, Journal of biomechanics)

   When adherent cells are subjected to uniaxial sinusoidal stretch at frequencies close to physiological, their body and their contractile stress fibers realign nearly perpendicularly to the stretch axis. A common explanation for this phenomenon is that stress fibers reorient along the direction where they are unaffected by the applied cyclic stretch and thus can maintain optimal (homeostatic) tensile force. The ability of cells to achieve tensional homeostasis in response to external disturbances is important for normal physiological functions of cells and tissues and it provides protection against diseases, including cancer and atherosclerosis. However, quantitative experimental data that support the idea that stretch-induced reorientation is associated with tensional homeostasis are lacking. We observed previously that in response to uniaxial cyclic stretch of 10% strain amplitudes, traction forces of single endothelial cells reorient in the direction perpendicular to the stretch axis. Here we carried out a secondary analysis of those data to investigate whether this reorientation of traction forces is associated with tensional homeostasis. Our analysis showed that stretch-induced reorientation of traction forces was accompanied by attenuation of temporal variability of the traction field to the level that was observed in the absence of stretch. These findings represent a quantitative experimental evidence that stretch-induced reorientation of the cell’s traction forces is associated with the cell’s tendency to achieve tensional homeostasis. 

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