טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentGeva Avner
SubjectSwelling of Bilayer Membranes under Decompression
and Ultrasound
DepartmentDepartment of Biomedical Engineering
Supervisor Professor Eitan Kimmel
Full Thesis textFull thesis text - English Version


Abstract

The use of ultrasound (US) for therapeutic purposes has been described extensively in the literature. The potential for ultrasound non-invasive treatments attracts a lot of interest, as well as the wide range therapeutic properties that result from ultrasound-tissue interaction. Nevertheless, the mechanism by which ultrasound affects cells and tissues is poorly understood.   Better understanding of this mechanism will improve applications of ultrasound in many medical fields such as imaging, drug delivery, non-invasive nerve stimulation and wound healing. 

A novel model, called the Bilayer Sonophore (BLS), suggests that ultrasound energy causes structural changes in the bilayer membrane of cells.  The model predicts that the oscillating ultrasound pressure wave results in periodic expansion and contraction of the intra-membrane space. According to the model, bilayer leaflets are pulled apart when negative pressures overcome the molecular attractive forces between the two leaflets, consequently driving dissolved gas diffusion into the intra-membrane space. During positive pressures, the leaflets are pushed back together and dissolved gas diffuses out of the intra-membrane space. In addition, a derivative of the BLS model predicts that decompression of bilayer membranes results in intra-membrane swelling.

The purpose of my work was to find evidence for bilayer leaflets separation under ultrasound treatment and decompression maneuver. Fluorescent-labeled liposomes were exposed to US, and study of fluorescent properties of the liposomes, such as Fluorescent Resonance Energy Transfer (FRET) and self-quenching, showed behavior that can be interpreted as average expansion of intra-membrane space that followed bilayer leaflets separation. In addition, Red Blood Cells (RBCs) of rats were decompressed and studied under Scanning Electron Microscopy (SEM), which showed first evidence for membrane swelling. Finally, a whole rat was decompressed. Histological studies of rat tissues showed damage to soft tissues of the brain and lungs, which could be the result of membrane swelling due to decompression effects.

Overall, in this work we developed tools that allow investigation of intra-membrane swelling under US and decompression treatments. The results strongly support the BLS model and this thesis opens doors for further research in the field.