The pursuit of a greater understanding of the biological membrane has led to the development of a number of mimetics and probing techniques. This thesis contributes to both of these efforts.
Towards the development of mimetics, poly(N-isopropylacrylamide) (pNIPAM) microgels were explored as membrane supports. PNIPAM microgels are “smart” materials that experience a volume phase transition (VPT) at ~32°C, where they undergo a severe loss in volume. The core-shell microgels were synthesized with a low crosslinked pNIPAM core covered by a highly crosslinked pNIPAM shell that was functionalized with exploitable carboxylates.
It was shown that a lipid bilayer could be coated on these microgels using either liposomes or bicelles. Specifically, lipid bilayer enclosed microgels made with liposomes (“Lipogels”) were created by using hydrophobically modified microgels, which possessed the ability to sequester liposomes that could ultimately be fused into a continuous bilayer. It was also found that above the VPT temperature, surface decoupled lipid protrude into highly curved structures. Hence, the VPT property could be used to control the curvature of the Lipogel bilayer. These particles could be useful platforms for conducting biophysical membrane studies as well as drug delivery vehicles.
Bicelles were also explored as lipid sources for microgel coating, resulting in the creation of “Bicellogels”. Electrostatic attraction between cationic bicelles and unmodified anionic core-shell pNIPAM microgels resulted in the coating of the latter. Astonishingly, the resulting bilayer was made up of only the long chain bicellar lipid. Due to the simplicity of this method, it could be extended to easily coat all types of soft material.
The last development on the pNIPAM front involved the coupling of intact liposomes to microgels to create “VESCOgels”. These complexes offer two distinct cargo holds through which temporally distinct release can be achieved. Hence, they could be very useful for applications in tandem release.
Lastly, the 31P CODEX NMR technique was adapted to study the lateral diffusion of phospholipids in large liposomes. This technique allows for the measurement of lateral diffusion coefficients of multiple phospholipids simultaneously. This could prove useful for the study of such biologically relevant phenomena as domain formations and drug-lipid interactions.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/65747 |
| Date | 01 September 2014 |
| Creators | Saleem, Qasim |
| Contributors | Macdonald, Peter |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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