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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 immune response to HIV infection

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   Conway, Jessica M.; Ribeiro, Ruy M. (December 2018, Current Opinion in Systems Biology)
3. Progerin-expressing endothelial cells are unable to adapt to shear stress

   https://doi.org/10.1016/j.bpj.2022.01.004  

   Danielsson, Brooke E.; Peters, Hannah C.; Bathula, Kranthi; Spear, Lindsay M.; Noll, Natalie A.; Dahl, Kris N.; Conway, Daniel E. (January 2022, Biophysical Journal)
4. Chromatin condensation regulates endothelial cell adaptation to shear stress

   https://doi.org/10.1091/mbc.E22-02-0064  

   Danielsson, Brooke E.; Tieu, Katie V.; Spagnol, Stephen T.; Vu, Kira K.; Cabe, Jolene I.; Raisch, Tristan B.; Dahl, Kris Noel; Conway, Daniel E. (September 2022, Molecular Biology of the Cell)

   Discher, Dennis (Ed.)

   Vascular endothelial cells (ECs) have been shown to be mechanoresponsive to the forces of blood flow, including fluid shear stress (FSS), the frictional force of blood on the vessel wall. Recent reports have shown that FSS induces epigenetic changes in chromatin. Epigenetic changes, such as methylation and acetylation of histones, not only affect gene expression but also affect chromatin condensation, which can alter nuclear stiffness. Thus, we hypothesized that changes in chromatin condensation may be an important component for how ECs adapt to FSS. Using both in vitro and in vivo models of EC adaptation to FSS, we observed an increase in histone acetylation and a decrease in histone methylation in ECs adapted to flow as compared with static. Using small molecule drugs, as well as vascular endothelial growth factor, to change chromatin condensation, we show that decreasing chromatin condensation enables cells to more quickly align to FSS, whereas increasing chromatin condensation inhibited alignment. Additionally, we show data that changes in chromatin condensation can also prevent or increase DNA damage, as measured by phosphorylation of γH2AX. Taken together, these results indicate that chromatin condensation, and potentially by extension nuclear stiffness, is an important aspect of EC adaptation to FSS. 

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5. The role of shear stress and altered tissue properties on endothelial to mesenchymal transformation and tumor-endothelial cell interaction

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   Mina, Sara G.; Huang, Peter; Murray, Bruce T.; Mahler, Gretchen J. (July 2017, Biomicrofluidics)