Modulation of the molecular arrangement in artificial and biological membranes by phospholipid-shelled microbubbles.
The transfer of material from phospholipid-coated microbubbles to cell membranes has been hypothesized to play a role in ultrasound-mediated drug delivery. In this study, we employed quantitative fluorescence microscopy techniques to investigate this phenomenon in both artificial and biological membrane bilayers in an acoustofluidic system. The results of the present study provide strong evidence for the transfer of material from microbubble coatings into cell membranes. Our results indicate that transfer of phospholipids alters the organization of molecules in cell membranes, specifically the lipid ordering or packing, which is known to be a key determinant of membrane mechanical properties, protein dynamics, and permeability. We further show that polyethylene-glycol, used in many clinical microbubble formulations, also has a major impact on both membrane lipid ordering and the extent of lipid transfer, and that this occurs even in the absence of ultrasound exposure.
Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford OX3 7DQ, United Kingdom.
Dario
D
Carugo
Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford OX3 7DQ, United Kingdom.
Miles
M
Aron
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, United Kingdom.
Erdinc
E
Sezgin
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, United Kingdom; Research Complex at Harwell, Central Laser Facility, Rutherford Appleton Laboratory, Science and Technology Facilities Council, Harwell, Oxford OX11 0FA, United Kingdom.
Jorge
J
Bernardino de la Serna
Department of Chemistry, Imperial College London, London SW7 2AZ, United Kingdom.
Marina K
MK
Kuimova
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, United Kingdom.
Christian
C
Eggeling
Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford OX3 7DQ, United Kingdom. Electronic address: Eleanor.stride@eng.ox.ac.uk.
Eleanor
E
Stride
D000162:Acoustics; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D003287:Contrast Media / Q000378:metabolism*; D004867:Equipment Design; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism*; D045423:Microbubbles; D010743:Phospholipids / Q000378:metabolism*; D013010:Sonication; D000069453:Ultrasonic Waves; D014463:Ultrasonography
D003287:Contrast Media; D008051:Lipid Bilayers; D010743:Phospholipids
Lipid order; Membrane bilayers; Microbubbles; Ultrasound