Permeability studies

What is permeability?

Biological permeability is the passage of molecules through a biological membrane or a barrier.
Cell membranes are selectively permeable, meaning that substances cannot cross the barrier indiscriminately. Polarity, hydrophobicity, charge, size and shape are some of the properties affecting permeability (1). Properties of the membrane itself are also important.

Permeability and transport studies are often performed with fluorescent dextran derivatives or other polysaccharides of various sizes. Florescent measurements can also provide qualitative data in real time with use of intravital fluorescence microscopy.

Different types of permeability studies

Permeability can be studied in cells, tissues, humans (non-clinical) and animals. Vascular permeability (2,3), glomerular filtration (4–6) and studies of the blood-brain barriers (7) have been studies with fluorescent derivatives from TdB Labs. Our dextran derivatives have also been utilized to study the permeability of keratin (8) and the epithelial (9–11) and mucosal (12,13) layer. The same products have also been used to study internal tissue (14,15), neural stem cells (16) as well as renal tissue (17).

Polysaccharides functionalised with carboxymethyl (CM)-or diethylaminomethyl (DEAE)-groups from TdB Labs have been used to study the effects of charge on permeability (18–20). Lysine modification provides tools for fixation and conjugation.

Microvascular flow and glomerular filtration

Movie. Microvascular flow and glomerular filtration are seen in a living rat kidney through the use of 150 kDa TRITC-dextran (red, microvascular flow) and a 4kDa FITC-dextran (green, glomerular filtration), both from TdB Labs. The initial part of the movie shows a glomerulus in the center and cross sections of surrounding tubules (orange); the nuclei in all cells appear cyan. The large 150 kDa TRITC-dextran is slowly infused in first, exhibiting spikes in fluorescence intensity as the material distributes throughout the bloodstream. After equilibration, the small 4kDa FITC-dextran is infused in and quickly filters across the glomerular filtration barrier and then travels along the proximal tubules surrounding the glomerulus.

References

Click to view references

1. Reece, J. B. & Campbell, N. A. Campbell biology. (Benjamin Cummings / Pearson., 2008).
2. Bulant, C. A., Blanco, P. J., Müller, L. O., Scharfstein, J. & Svensjö, E. Computer-aided quantification of microvascular networks: Application to alterations due to pathological angiogenesis in the hamster. Microvasc. Res. 112, 53–64 (2017).
3. Nascimento, C. R. et al. Mast Cell Coupling to the Kallikrein–Kinin System Fuels Intracardiac Parasitism and Worsens Heart Pathology in Experimental Chagas Disease. Front. Immunol. 8, (2017).
4. Asgeirsson, D., Venturoli, D., Fries, E., Rippe, B. & Rippe, C. Glomerular sieving of three neutral polysaccharides, polyethylene oxide and bikunin in rat. Effects of molecular size and conformation. Acta Physiol. 191, 237–246 (2007).
5. Dolinina, J., Sverrisson, K., Rippe, A., Öberg, C. M. & Rippe, B. Nitric oxide synthase inhibition causes acute increases in glomerular permeability in vivo, dependent upon reactive oxygen species. Am. J. Physiol.-Ren. Physiol. 311, F984–F990 (2016).
6. Rippe, C., Asgeirsson, D., Venturoli, D., Rippe, A. & Rippe, B. Effects of glomerular filtration rate on Ficoll sieving coefficients (θ) in rats. Kidney Int. 69, 1326–1332 (2006).
7. Gustafsson, S. et al. Blood-brain barrier integrity in a mouse model of Alzheimer’s disease with or without acute 3D6 immunotherapy. Neuropharmacology 143, 1–9 (2018).
8. Navarro, J., Swayambunathan, J., Lerman, M., Santoro, M. & Fisher, J. P. Development of keratin-based membranes for potential use in skin repair. Acta Biomater. 83, 177–188 (2019).
9. Bücker, R. et al. Campylobacter jejuni impairs sodium transport and epithelial barrier function via cytokine release in human colon. Mucosal Immunol. 11, 474–485 (2018).
10. Propheter, D. C., Chara, A. L., Harris, T. A., Ruhn, K. A. & Hooper, L. V. Resistin-like molecule β is a bactericidal protein that promotes spatial segregation of the microbiota and the colonic epithelium. Proc. Natl. Acad. Sci. U. S. A. 114, 11027–11033 (2017).
11. Bowie, R. V. et al. Lipid rafts are disrupted in mildly inflamed intestinal microenvironments without overt disruption of the epithelial barrier. Am. J. Physiol.-Gastrointest. Liver Physiol. 302, G781–G793 (2012).
12. Lee, S. et al. Arhgap17, a RhoGTPase activating protein, regulates mucosal and epithelial barrier function in the mouse colon. Sci. Rep. 6, 26923 (2016).
13. Dolowschiak, T. et al. IFN-γ Hinders Recovery from Mucosal Inflammation during Antibiotic Therapy for Salmonella Gut Infection. Cell Host Microbe 20, 238–249 (2016).
14. Torge, A., Pavone, G., Jurisic, M., Lima-Engelmann, K. & Schneider, M. A comparison of spherical and cylindrical microparticles composed of nanoparticles for pulmonary application. Aerosol Sci. Technol. 53, 53–62 (2019).
15. Epple, H.-J. et al. Architectural and functional alterations of the small intestinal mucosa in classical Whipple’s disease. Mucosal Immunol. 10, 1542–1552 (2017).
16. Zhu, C., Mahesula, S., Temple, S. & Kokovay, E. Heterogeneous Expression of SDF1 Retains Actively Proliferating Neural Progenitors in the Capillary Compartment of the Niche. Stem Cell Rep. 12, 6–13 (2019).
17. Palygin, O. et al. Essential role of Kir5.1 channels in renal salt handling and blood pressure control. JCI Insight 2,.
18. Srikantha, N. et al. Influence of molecular shape, conformability, net surface charge, and tissue interaction on transscleral macromolecular diffusion. Exp. Eye Res. 102, 85–92 (2012).
19. Asgeirsson, D., Venturoli, D., Rippe, B. & Rippe, C. Increased glomerular permeability to negatively charged Ficoll relative to neutral Ficoll in rats. Am. J. Physiol.-Ren. Physiol. 291, F1083–F1089 (2006).
20. Stewart, S. E. et al. The Perforin Pore Facilitates the Delivery of Cationic Cargos. J. Biol. Chem. 289, 9172–9181 (2014).

 

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