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Review
. 2021 Jul 3;9(3):1904773.
doi: 10.1080/21688370.2021.1904773. Epub 2021 May 18.

Surface charge, glycocalyx, and blood-brain barrier function

Affiliations
Review

Surface charge, glycocalyx, and blood-brain barrier function

Fruzsina R Walter et al. Tissue Barriers. .

Abstract

The negative surface charge of brain microvessel endothelial cells is derived from the special composition of their membrane lipids and the thick endothelial surface glycocalyx. They are important elements of the unique defense systems of the blood-brain barrier. The tissue-specific properties, components, function and charge of the brain endothelial glycocalyx have only been studied in detail in the past 15 years. This review highlights the importance of the negative surface charge in the permeability of macromolecules and nanoparticles as well as in drug interactions. We discuss surface charge and glycoxalyx changes in pathologies related to the brain microvasculature and protective measures against glycocalyx shedding and damage. We present biophysical techniques, including a microfluidic chip device, to measure surface charge of living brain endothelial cells and imaging methods for visualization of surface charge and glycocalyx.

Keywords: Blood-brain barrier; drug delivery; glycocalyx; nanoparticles; surface charge.

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Figures

Figure 1.
Figure 1.
A. Structure of the lipid membrane of cells: headgroups of lipid species with negative charge are shown in red shades. B. Structure of the endothelial cell surface glycocalyx: core proteins are shown in green shades, negatively charged glucosaminolgycans and sialic acid are shown in red shades. Abbreviations: CD44: cluster of differentiation 44 glycoprotein, also known as hyaluronic acid receptor; CS: chondroitin sulfate; HA: hyaluronic acid; HS: heparan sulfate; SA: sialic acid
Figure 2.
Figure 2.
Modification of cellular surface charge by the insertion of a cationic and lipophilic molecule (blue) to the plasma membrane or by enzymatic cleavage of negatively charged residues from the surface glycocalyx (red shades)
Figure 3.
Figure 3.
Laser-Doppler velocimetry and streaming potential to measure the zeta potential of brain endothelial cells (modified from)

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