טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentRam-on Maor
SubjectNanostructural Study of Double-Tailed Amphiphiles and
Oppositely Charged Polyelectrolytes Complexes
DepartmentDepartment of Nanoscience and Nanotechnology
Supervisor Professor Emeritus Yeshayahu Talmon
Full Thesis textFull thesis text - English Version


Abstract

The interactions between polyelectrolytes and low molecular weight amphiphiles are a widely investigated subject due to its importance in many applications. Many industrial formulations, like water-based paints, detergents, and cosmetic products, which contain water-soluble polymers and surfactants. In biotechnological applications and in biological systems, the interactions between polar lipids and different macromolecules are most significant.

Polyelectrolyte/amphiphile systems have been extensively studied in the last decades, focusing on surfactant micelles as the surfactant aggregate in the interaction; polyelectrolytes and vesicles interactions received much less attention. Double-tailed amphiphiles and lipids induce formation of vesicles, namely, spherical structures composed of a bilayer folded over itself, entrapping part of the solvent. Their ability to encapsulate substances and to form complexes with other molecules makes them attractive for many applications such as drug delivery. Their potential to be used as non-viral gene delivery vectors contributes to the extensive research in DNA and lipids complexes (lipoplexes). However, their disintegration in the presence of blood-serum raises questions about their stability. In our work we focused on complexes formed between double-tailed cationic amphiphiles and oppositely-charged polyelectrolytes, because they serve as model complexes for gene delivery.

In our research we applied cryogenic-transmission electron microscopy (cryo-TEM) for the nanostructural characterization of amphiphile/polyelectrolyte complexes. We investigated the effect of varying system parameters on the nanostructures. We also performed small-angle x-ray scattering (SAXS) measurements to provide quantitative information and to support the imaging.

Both cryo-TEM and SAXS showed the strong effect of changing system parameters on the complex morphology. We showed the major influence of the polyelectrolyte stiffness on the periodic distance of the multilamellar complex, while we observed that molecular weight did not lead to evident change. Moreover, in weak-acid polyelectrolytes pH was found to have substantial effect on the complex formation. Further work was conducted to understand the complexes interactions with blood-serum proteins, particularly with bovine serum albumin (BSA), and to elucidate why the lipoplexes disassociate when introduced into the blood. Cryo-TEM provided a clear and direct look on the nanostructures obtained, and demonstrated under what conditions the complexes promote the release of the polyelectrolyte.

The structural transition in the nerve axon myelin sheath was studied by SAXS and cryo-TEM to evaluate and characterize the influence of lipid composition and protein content on the complex morphology. We also examined the influence of salt concentration on the self-assembly of the complexes. The results of this work are directly connected to Multiple Sclerosis (MS) etiology, and may suggest new avenues for treatment and diagnosis.