טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentShapira Einat
SubjectMolecular Dynamics Simulations of Nanobubbles Interaction
with Lipid Structures
DepartmentDepartment of Nanoscience and Nanotechnology
Supervisor Professor Emeritus Eitan Kimmel


Abstract

Cavitation in-vivo, formation of bubbles in the body, is usually associated with decompression sickness and high-intensity ultrasound. Cavitation bubbles are believed to incept from pre-existing nanometric gas nuclei. However, the location of these nuclei in tissues and the mechanism of the bubbles’ growth remain unknown. Moreover, traces of cavitation activity also appear in low-intensity ultrasound, which is considered non-cavitational. The involvement of the bilayer membrane in most (if not all) cavitation incidents led to the formulation of the bilayer sonophore model. In the framework of the bilayer sonophore model, a thin air layer compartment lies between the two leaflets of the membrane, and cavitation occurs in the intra-membrane space. The aim of the current research is to investigate the hypothesis that cavitation nuclei are localized in the bilayer membrane.

To investigate our hypothesis, we used molecular dynamics simulations. Molecular dynamics is a tool that allows investigation of the nanometric scale in times scales of up to a few microseconds. It incorporates molecular interactions, both mechanistic and electric. By integrating Newton’s equation of motion, the temporal evolution of a system is explored. In combination with a well-known coarse-grained model for bio-molecules (the MARTINI model), we modeled a gas particle that mimics physical properties of air, mainly: density and compressibility in a range of temperatures and pressures, as well as solvation energies in a variety of solvents. We then simulated this gas particle, together with water, surfactants and lipid molecules, to research the behavior of gas clusters in these systems.

We show that gaseous nanobubbles have a unique density behavior. The smaller the number of gas particles in the bubble, the greater the gas density inside. We show that nanobubbles will form on a hydrophobic solid surface, but not on a hydrophilic one. Both these results are in accord with the literature. We further show that gas density in the nanobubble is affected by the presence of surfactants that reduce surface tension. In addition, we show that nanobubbles transition into lipid membranes, and that this interaction is affected by the type of lipid and configuration of the membrane. Finally, we demonstrate how the presence of nanobubbles in these systems is reducing the required energy and pressure for cavitation.

We believe this model can be extended in many directions to account for nanobubbles interaction with more complex membranes, transmembrane proteins, DNA and ions. Questions of stability and the effect of temperature or pressure can be addressed as well. Importantly, this model can be used to explore the transition of a nanobubble to a microbubble under negative pressure. We believe the role of the nanoscopic bubbles in mammal’s biology is yet to be discovered.