Tuning the lipid bilayer: the influence of small molecules on domain formation and membrane fusion

Rianne Bartelds

Research output: ThesisThesis fully internal (DIV)

1192 Downloads (Pure)

Abstract

The eukaryotic cell membrane is a highly regulated, heterogeneous lipid bilayer that embeds transport, receptor and channel proteins as well as membrane-bound enzymes. The membrane is thought to have domains, named rafts. Proteins associate with rafts or are excluded, which brings proteins together or isolates them from others.
Since these rafts are very small and short-lived, model membranes have been developed to study lipid-lipid interactions and protein partitioning. One of these model membrane systems are giant unilamellar vesicles (GUVs), micrometer-size vesicles that can be studied by light microscopy. Three component GUVs consisting of a saturated lipid, an unsaturated lipid and cholesterol can phase separate into a dense liquid-ordered (Lo) and more fluid liquid-disordered (Ld) phase.
In this thesis, I have shown that small molecules such as some sugars, specific hydrocarbons and certain lipids influence the phase separation of this model membrane. The partitioning of the model peptide WALP in the Lo and Ld phase is described.
The second part of this thesis focuses on small vesicles, so-called large-unilamellar vesicles (LUVs). Vesicles made from non-ionic surfactants, single-chain amphiphiles, were characterized. These molecules are shown to form closed, stable vesicles that may be a cost-effective alternative for already existing liposome-based drug formulations.
Membrane fusion requires a delicate balance between disturbing the membrane, needed for fusion, and minimizing content leakage. I show that non-leaky fusion with relatively high yields can be obtained using a commercially available enzyme that cuts off a fraction of lipid head groups.
Translated title of the contributionDe lipide bilagen beinvloeden: het effect van kleine moleculen op de vorming van domeinen en membraanfusie
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Groningen
Supervisors/Advisors
  • Poolman, Berend, Supervisor
Award date16-Feb-2018
Place of Publication[Groningen]
Publisher
Print ISBNs978-94-034-0371-7
Electronic ISBNs978-94-034-0370-0
Publication statusPublished - 2018

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