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Modulation of brain endothelial surface charge changes the transfer of charged molecules and targeted nanoparticles

Aug 30 - szerda

14:54 – 15:12

Sejtanalitika biofizikai megközelítéssel

E35

Modulation of brain endothelial surface charge changes the transfer of charged molecules and targeted nanoparticles

Mária Mészáros1, Szilvia Veszelka1,2, Fruzsina R Walter1,2, András Kincses1, Sándor Valkai1, András Dér1, Mária A Deli1

1 Institute of Biophysics, Biological Research Centre, Szeged

The highly negative surface charge of brain endothelial cells is part of the blood-brain barrier (BBB)defense systems. It is derived from charged membrane lipids and the endothelial surface glycocalyx. We showed that physiological factors inducing BBB properties (co-culture, fluid flow, targeting signaling pathways) increase the surface glycocalyx thickness and makes the zeta potential of the cells more negative measured by laser-Doppler velocimetry (LDv).

Zeta potential by LDv can only be measured on cells in suspension, so we designed and fabricated a novel lab-on-a-chip (LOC) device to monitor streaming potential parallel to the surface of confluent cell layers. Streaming potential measured on brain endothelial cell monolayers in the LOC device were recorded and verified by comparing to zeta potential results measured by LDv and model simulations. Changes in the negative surface charge of the BBB model by neuraminidase (cleaving negatively charged sialic acid residues from the glycocalyx) or lidocaine (interacts with lipid membranes) could be measured by both the LOC device and LDv.

Lidocaine, a cationic and lipophilic anesthetic and antiarrhythmic drug turned more positive the negative zeta potential of brain endothelial cells. It also decreased the flux of a cationic lipophilic molecule (rhodamine 123) across the BBB model without changing the penetration of hydrophilic neutral or negatively charged markers. Neuraminidase and the cationic lipid TMA-DPH, which elevated the surface charge, increased the uptake of vesicular nanoparticles targeted by alanine and glutathione in brain endothelial cells.

In conclusion, the negative surface charge of brain endothelial cells is a fundamental BBB property. It is important in the transfer of charged molecules and the uptake mechanism of charged nanoparticles and can be modulated by modification of plasma membrane lipid composition or the glycocalyx.