Introduction Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid with known paradoxical effects on endothelial cell (EC) barrier regulation. S1P binds 5 GPCRs: S1PR1 (Endothelial differentiation gene (EDG)-1), S1PR2 (EDG-5), S1PR3 (EDG-3), S1PR4 (EDG-6), and S1PR5 (EDG-8). Despite the aliases, endothelial cells predominantly express S1PR1&3. S1PR1 has been shown to have barrier protective or enhancing effects on…
Introduction Read the manuscript here: Integrative Biology Publication Please refer to the linked manuscript for a detailed introduction. In short, we have been interested in characterizing the role of endothelial cell (EC) apicobasal polarity in inflammation. While usually reserved for the epithelium, ‘apicobasal polarity’ is a term describing a monolayer or cell with defined apical…
Introduction In our labs previously work, difficulties in growing endothelial cells (ECs) under shear flow lead to the exploration of novel membrane technologies that permit firm EC attachment, without compromising membrane permeability or leukocyte transmigration studies. We ultimately landed on the development of effectively ‘dual-scale’ membranes that contained 3 μm pores dispersed amongst an NPN…
Background Previously we characterized HUVEC monolayer barrier via TEER in traditional transwell systems following polarized TNF-alpha exposure (Figure 1). One major shortcoming of this experimental set up for our study is it does not accurately reflect the permeability of HUVECs within our uSiM system (where all other experiments were performed). Thus, a couple reviewers wanted…
Introduction Much of the background information for this set of experiments can be found in my previous post. In short, endothelial cells mainly express two receptors to the sphingolipid S1P, S1PR1 and S1PR3. S1PR1 is characterized as a barrier enhancing signaler, while S1PR3 appears to elevate vascular permeability while promoting leukocyte capture. Based on TEER…
Introduction Sphingosine-1-phosphate: production and endothelial cell signaling Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid produced through the phosphorylation of sphingosine, a component of the plasma membrane, by SphK1/2. Many cells produce and store S1P, the largest source of which is platelets, due to their high native SphK activity. Erythrocytes and leukocytes are also sources of S1P…
Introduction EC Apicobasal polarity in immunity has and will continue to be a theme of my thesis. I have presented on bits and pieces of this work over the past year or so, but now that this work is under review and more or less complete pending reviewer comments, I wanted to summarize our finds…
Summary After success with the development and execution of the μSiM-CA (Canalicular Array; see Masters et al., Nanomedicine: Nanotechnology, Biology, and Medicine 2019), Jim wanted to develop a platform to answer some more biophysics focused questions. In order to facilitate these studies, the platform would ideally be configured to allow for live imaging of staph…
Introduction In an effort to move forward with a ‘lung microvasculature on a chip’ model, I have been experimenting with using primary human pulmonary microvascular endothelial cells in our devices. The cells (HPMECs) are purchased from Promocell and are collected from a single donor lung. Unfortunately I found little information on their use in recent…
Introduction Sepsis related projects had a decent presence at this years Biomedical Engineering Society (2019). I will detail a few of the talks I found most relevant to our group and research. Nanomedicine for Acute Criticial Illness by Dr. Jacob Brenner (U Penn Medical) Dr. Brenner is a practicing physician working on ICAM-1, PECAM-1, and…