Year: 2020
Type: article
Abstract: Disruption of plasma membrane integrity is a primary mechanism of nanoparticle toxicity in cells.Mechanistic studies on nanoparticle-induced membrane damage have been commonly performed using model membranes with a focus on symmetric bilayers, overlooking the fact that the membrane has an asymmetric phospholipid composition.In this thesis, erythrocytes with normal and scrambled membrane asymmetry were utilized to examine how loss of membrane asymmetry and the resulting alterations in the outer leaflet lipid composition affect nanoparticle-membrane interactions.Loss of membrane asymmetry was achieved by induction of eryptosis, using a calcium ionophore.Erythrocyte membrane disruption (hemolysis) by plain silica nanoparticles was significantly reduced in eryptotic compared to healthy cells.In agreement, a significant reduction in nanoparticle binding to the membrane was observed upon loss of membrane asymmetry.The particles also caused significant cell deformation, changing healthy erythrocytes into a spheroid shape.In agreement with findings in cells, plain particles disrupted lipid vesicles mimicking the erythrocyte outer leaflet lipid composition.The degree of disruption, and nanoparticle binding to the membrane, was reduced in vesicles mimicking the composition of scrambled membranes.Together, findings indicate an important role for the lipid composition of the membrane outer leaflet in nanoparticleinduced membrane damage in both lipid vesicles and erythrocytes.
Author: Bigdelou, Parnian
Institution: Ohio University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funder: Division of Graduate Education
OpenAlex ID: W6987050856