La Trobe
38083_SOURCE01_3_A.pdf (12.29 MB)

A structural study of liposome formation

Download (12.29 MB)
posted on 2023-01-18, 17:45 authored by Muhammad Shamsul Huda Mubin
Submission note: A thesis submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Chemistry, Faculty of Science, Technology & Engineering, La Trobe University, Melbourne.

Liposomes are self-assembled phospholipid bilayer vesicles which are equally important for basic research and application in chemistry, biochemistry and biophysics. Whereas liposomes are already in extensive use in a range of areas, curiously some basic properties of thermodynamic relevance are yet to be described unambiguously. In this thesis I investigated temporal and thermal behavior of liposomes made of three different lipid compositions including (i) dimyristoylphosphatidylcholine (DMPC), (ii) mixture of DMPC and cholesterol, and (iii) DMPC and dimyristoylphsophatidylglycerol (DMPG). By using dynamic light scattering I demonstrated that, at normal human body temperature, equilibrium size distributions of liposomes evolve over time. The time needed for achieving equilibrium sizes varied depending on the compositions of the lipids. Liposome sizes decrease towards equilibrium for neat DMPC and a mixture of DMPC and cholesterol. In contrast, size distributions of liposomes made of DMPC mixed with 25% DMPG increase to some extent before achieving equilibrium. DMPC/DMPG liposomes showed reproducible size trends at higher (above 250C) temperatures upon temperature ramping between 17-37 0C in spite of a degree of fluctuations near the main phase transition temperature. Stable size distributions were typically bimodal. The possibility of lipid mimetic luminescent labelling of phospholipid membranes for microscopic imaging of liposomes aggregates was also investigated. Two lipid mimetic ruthenium and iridium complexes, which have two alkyl chains of nine carbons, were successfully incorporated into phospholipid membranes. Control experiments with their analogues, one hydrophilic and the other lipohilic, proved that the lipid mimetic metal complexes are indeed lipid mimetic. Fluorescent microscopic imaging revealed that only 0.5 mole % (relative to lipid) of these complexes already provided sufficient luminescence for optical imaging of liposomes. Confocal laser microscopic imaging of labelled liposomes yielded unprecedented structural detail revealing that inter bilayer attraction between lipid structure is stronger than the Coulombic repulsion from the head group charges. Synchrotron small angle X-ray scattering data showed that the use of luminescent ruthenium and iridium complexes for labelling liposomes did not change the lamellar spacing of lipid membranes. Thus a truly biomimetic labelling was achieved.


Center or Department

Faculty of Science, Technology and Engineering. School of Chemistry.

Thesis type

  • Ph. D.

Awarding institution

La Trobe University

Year Awarded


Rights Statement

This thesis contained third party copyright material which has been removed. The thesis author retains all proprietary rights (such as copyright and patent rights) over all other content of this thesis, and has granted La Trobe University permission to reproduce and communicate this version of the thesis. The author has declared that any third party copyright material contained within the thesis made available here is reproduced and communicated with permission. If you believe that any material has been made available without permission of the copyright owner please contact us with the details.

Data source

arrow migration 2023-01-10 00:15. Ref: latrobe:38083 (9e0739)

Usage metrics

    Open Theses


    No categories selected



    Ref. manager