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Principal Investigator: Monica Maki Burdick
Organization: OHIO UNIVERSITY ATHENS
Fiscal Year: 2019
Award: $428,636
Funding agency: National Institute of Environmental Health Sciences
Abstract!
Engineered nanomaterials (ENMs) are being increasingly used in industrial and biomedical applications. It is
estimated that there are currently more than 1,800 nanomaterial-based products on the market, with more than
770 in the United States alone. This widespread use has raised concerns regarding the potential health hazards
of ENMs. One important aspect of toxicity of ENMs is their interaction with the plasma membrane of mammalian
cells. The plasma membrane is the first cellular entity that "meets" ENMs and has been suggested to play a major
role in ENM-induced cytotoxicity. Over the past decade, a number of studies have utilized simple membrane
models, such as phospholipid vesicles, to gain mechanistic information on ENM-membrane interactions.
However, the plasma membrane is an asymmetric lipid structure with a diverse array of lipids and proteins;
therefore, studies with simple membrane models do not provide a comprehensive understanding of ENM-
membrane interactions in live cells. The current application aims to provide a mechanistic understanding of the
role of membrane lipid asymmetry and membrane proteins, in modulating ENM-membrane interactions. Using
vesicles that mimic the asymmetry of the cell plasma membrane, as well as biologically-relevant vesicles that are
isolated from the membrane, this application aims to investigate the role of membrane asymmetry and membrane
proteins in how ENMs with different surface properties and protein corona bind to the plasma membrane,
internalize in cells, and alter plasma membrane structure and integrity. The information generated from this work
is expected to elucidate the role of the plasma membrane structure and composition in ENM-membrane
interactions, facilitate the development of more physiologically relevant membrane models for mechanistic
studies, and reveal the role of particle physicochemical properties and protein corona in their interactions with the
cell plasma membrane. The knowledge base created from this work will significantly enhance the fields of
particle-mediated drug delivery and environmental health and safety of ENMs.
Terms: <Artificial Membranes><Binding><Biological><Blood Plasma Cell><Blood erythrocyte><Cell Body><Cell Membrane Lipids><Cell membrane><Cells><Cristobalite><Cytoplasm><Cytoplasmic Membrane><Data><Development><Drug Delivery><Drug Delivery Systems><Engineering><Environment><Environmental Health><Environmental Health Science><Erythrocyte Cytoskeleton><Erythrocyte Membrane><Erythrocytes><Erythrocytic><Exposure to><Goals><Guidelines><Health Hazards><Hemolysis><Individual><Industrialization><Life><Lipid Bilayers><Lipids><Lytotoxicity><Mammalian Cell><Marrow erythrocyte><Mediating><Membrane><Membrane Lipids><Membrane Protein Gene><Membrane Proteins><Membrane-Associated Proteins><Modeling><Molecular Interaction><Ohio><Phosphatides><Phospholipids><Physiologic><Physiological><Plasma Cells><Plasma Membrane><Plasmacytes><Play><Property><Proteins><Red Blood Cells><Red Cell><Research><Role><Safety><Sand><Silica><Silicon Dioxide><Structure><Surface Properties><Surface Proteins><Testing><Toxic effect><Toxicities><Tridymite><United States><Universities><Vesicle><Work><base><blood corpuscles><consumer product><cytotoxicity><developmental><erythrolysis><graduate student><insight><knowledge base><knowledgebase><lipid bilayer membrane><lipid structure><membrane model><membrane structure><nano materials><nano particle><nano-sized particle><nanomaterials><nanoparticle><nanosized particle><particle><plasmalemma><plasmocyte><safety engineering><social role><tool><undergraduate><undergraduate student>