Fluorescence microscopy studies of interactions between monomeric α-Synuclein and lipid membranes

Alexandra Andersson

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

105 Nedladdningar (Pure)

Sammanfattning

α-Synuclein (α-Syn), is an intrinsically disordered protein present in the substantia nigra part of the brain. α-Syn is commonly known to associate with lipid membranes containing anionic lipids. Hence, the protein is hypothesized to be involved in the vesicle trafficking at the synapses, but there are yet many unanswered questions regarding the full physiological role of the protein. During the degenerative pathway of Parkinson’s disease, α-Syn misfolds and forms fibrillar aggregates. Together with lipids, α-Syn fibrils form Lewy body inclusions, a known hallmark for Parkinson’s disease and other synucleopathies. The aim of this thesis has been to study interactions between monomeric α-Syn and lipid membranes, to obtain a better understanding of both the physiological and pathological role of α-Syn.
This thesis has been focused on studying interactions between monomeric α-Syn and different lipid membranes using single vesicle and single protein imaging techniques, to be able to study individual events that otherwise might disappear in a bulk average. The results show that the protein binds cooperatively to both vesicles and supported lipid bilayers in conditions with an excess of lipid membrane. The binding lifetime of α-Syn varies from ms to seconds or longer,
depending on the overall protein concentration and the relation between lipids and proteins in the system. Further, a high density of bound α-Syn might deform the membrane and lead to fission of vesicles, depending on the lipid composition of the membrane. However, association only occurs at sufficient membrane charge density, which also limits the number of protein
being adsorbed to the membrane.
Originalspråkengelska
KvalifikationDoktor
Tilldelande institution
  • Naturvetenskapliga fakulteten
Handledare
  • Jönsson, Peter, handledare
  • Sparr, Emma, Biträdande handledare
  • Snogerup-Linse, Sara, Biträdande handledare
  • Fornasier, Marco, Biträdande handledare
Sponsorer för avhandling
Tilldelningsdatum2023 okt. 20
UtgivningsortLund
Förlag
ISBN (tryckt)978-91-7422-972-1
ISBN (elektroniskt)978-91-7422-973-8
StatusPublished - 2023 sep. 4

Bibliografisk information

Defence details
Date: 2023-10-20
Time: 09:00
Place: Kemicentrum, KC:A, Lund University
External reviewer(s)
Name: Lundmark, Richard
Title: Professor
Affiliation: Umeå universitet
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Ämnesklassifikation (UKÄ)

  • Biofysik

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