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

• Published in: Ultrasonics 2014-12, Vol.54 (8), p.2090-2098
• Main Authors: Ibsen, Stuart, Shi, Guixin, Schutt, Carolyn, Shi, Linda, Suico, Kyle-David, Benchimol, Michael, Serra, Viviana, Simberg, Dmitri, Berns, Michael, Esener, Sadik
• Format: Article
• Language: English
• Subjects: Antigens, Neoplasm - chemistry; Cell Adhesion Molecules - chemistry; Cell Culture Techniques; Cell Membrane; Endothelium, Vascular - cytology; Epithelial Cell Adhesion Molecule; Equipment Design; Humans; Lecithins - chemistry; Lipid debris; Lipids - chemistry; Membrane Proteins - chemistry; Microbubble; Microbubble targeting; Microbubbles; Microscopy, Fluorescence; Molecular Imaging - methods; Peptides, Cyclic - chemistry; Phosphatidylcholines - chemistry; Phosphatidylethanolamines - chemistry; Polyethylene Glycols - chemistry; Ultrasonics; Ultrasound molecular imaging; Umbilical Veins - cytology
• ISSN: 0041-624X; 1874-9968
• DOI: 10.1016/j.ultras.2014.06.020

•Microbubbles successfully attached to the cell surface using targeting ligands.•Ultrasound exposure fragmented the microbubble lipid monolayer.•Lipid fragments from the monolayer remained adhered to the cell surface.•Fragments did not incorporate into the cell lipid membrane over a period of 96min.•Fragments translated and rotated across the cell surface as the cells migrated. 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.