Computationally designing a fluorescent probe to detect lipid membrane phase changes

Winslow, M. ORCID: 0000-0003-1985-0905, 2022. Computationally designing a fluorescent probe to detect lipid membrane phase changes. PhD, Nottingham Trent University.

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Lipid membranes are responsible for the regulation of many key cellular processes. Some of these processes, such as signalling events, are thought to be induced by the presence of lipid rafts. Observation of rafts in vivo has therefore been a key area of research to gain a better insight to the existence and function of membrane rafts. One promising technique is the use of fluorescent molecular probes designed to report on phase changes within a lipid membrane. In this work, a computational protocol to investigate a novel probe of membrane phase has been developed. In this approach, spin-flip time-dependent density functional theory is carefully calibrated and employed to investigate conical intersections to understand the restriction of intramolecular movement mechanism, whereby the fluorescence of a molecule is dependent upon the freedom of rotation around a bond responsible for the access of non-radiative decay pathways.

The probes tested in this study are methyl derivatives of 1,6-diphenylhexatriene and applied to quantum mechanics/molecular mechanics simulations of raft and non-raft environments, along with a preliminary study of molecules which could act as delivery vessels in vivo. It was found that the key dihedral angle of the 2-methyl derivative (2Me) could rotate sufficiently for non-radiative decay in the liquid-disordered non-raft environment whereas rotation was inhibited in the liquid-ordered raft environment promoting fluorescence making 2Me an ideal candidate for a simple phase sensitive fluorescent membrane probe.

Item Type: Thesis
Creators: Winslow, M.
Date: September 2022
Rights: The copyright in this work is held by the author. You may copy up to 5% of this work for private study, or personal, non-commercial research. Any re-use of the information contained within this document should be fully referenced, quoting the author, title, university, degree level and pagination. Queries or requests for any other use, or if a more substantial copy is required, should be directed to the author.
Divisions: Schools > School of Science and Technology
Record created by: Linda Sullivan
Date Added: 05 May 2023 09:27
Last Modified: 05 May 2023 09:27

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