The behavior of lipid debris left on cell surfaces from microbubble based ultrasound molecular imaging.

Viviana M Serra Lopez's picture
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TitleThe behavior of lipid debris left on cell surfaces from microbubble based ultrasound molecular imaging.
Publication TypeJournal Article
Year of Publication2014
AuthorsIbsen, S, Shi, G, Schutt, C, Shi, L, Suico, K-D, Benchimol, M, Serra, V, Simberg, D, Berns, M, Esener, S
JournalUltrasonics
Volume54
Issue8
Pagination2090-8
Date Published2014 Dec
ISSN1874-9968
KeywordsAntigens, Neoplasm, Cell Adhesion Molecules, Cell Culture Techniques, Cell Membrane, Endothelium, Vascular, Equipment Design, Humans, Lecithins, Lipids, Membrane Proteins, Microbubbles, Microscopy, Fluorescence, Molecular Imaging, Peptides, Cyclic, Phosphatidylcholines, Phosphatidylethanolamines, Polyethylene Glycols, Ultrasonics, Umbilical Veins
Abstract

Lipid monolayer coated microbubbles are currently being developed to identify vascular regions that express certain surface proteins as part of the new technique of ultrasound molecular imaging. The microbubbles are functionalized with targeting ligands which bind to the desired cells holding the microbubbles in place as the remaining unbound microbubbles are eliminated from circulation. Subsequent scanning with ultrasound can detect the highly reflectant microbubbles that are left behind. The ultrasound scanning and detection process results in the destruction of the microbubble, creating lipid fragments from the monolayer. Here we demonstrate that microbubbles targeted to 4T1 murine breast cancer cells and human umbilical cord endothelial cells leave behind adhered fragments of the lipid monolayer after exposure to ultrasound with peak negative pressures of 0.18 and 0.8MPa. Most of the observed fragments were large enough to be resistant to receptor mediated endocytosis. The fragments were not observed to incorporate into the lipid membrane of the cell over a period of 96min. They were not observed to break into smaller pieces or significantly change shape but they were observed to undergo translation and rotation across the cell surface as the cells migrated over the substrate. These large fragments will apparently remain on the surface of the targeted cells for significant periods of time and need to be considered for their potential effects on blood flow through the microcapillaries and potential for immune system recognition.

DOI10.1016/j.ultras.2014.06.020
Alternate JournalUltrasonics
PubMed ID25059435
PubMed Central IDPMC4151124
Grant List5U54CA119335-05 / CA / NCI NIH HHS / United States
P30 CA023100 / CA / NCI NIH HHS / United States
P30 CA23100 / CA / NCI NIH HHS / United States
R25 CA153915 / CA / NCI NIH HHS / United States
R25 CA153915 / CA / NCI NIH HHS / United States
T32 CA121938 / CA / NCI NIH HHS / United States
T32 CA121938 / CA / NCI NIH HHS / United States
U54 CA119335 / CA / NCI NIH HHS / United States