Design Principles of a Responsive Cell Membrane

Ph. D. Nataliya Safronova

AutorIn

Ph. D. Nataliya Safronova

Titel

Design Principles of a Responsive Cell Membrane

Zitierfähige Url:

https://nbn-resolving.org/urn:nbn:de:bsz:14-qucosa2-818465

Erstveröffentlichung

2022

Datum der Einreichung

19.12.2021

Datum der Verteidigung

23.08.2022

Abstract (EN)

Cell membranes are essential to life. All living organisms adapt their membranes in response to environmental perturbations to maintain optimal membrane function. However, the principles underlying membrane lipid composition and membrane adaptation remain poorly understood. Deciphering the functional basis for the lipidome complexity employed by cellular life is central to the problem of understanding principles of cell membrane organization, and is currently limited by the staggering complexity of biomembranes, as well as by the limited tools for membrane lipidome manipulation in vivo. My PhD project was designed to bridge this gap through exploring how lipidome size and complexity define cell membrane organization and bioactivity. To achieve the overarching goal, we have created a minimal membrane model system using one of the simplest self-replicating organisms – the mammalian pathogen Mycoplasma. By taking advantage of Mycoplasma’s limited biosynthetic machinery we have established a method of controlling membrane lipid composition in M. mycoides and its synthetic counterpart JCVI Syn3, and have showed that we can finely tune Mycoplasma membrane lipidome through lipid diet. By utilizing our membrane model system in our manuscript, we showed that Mycoplasma membranes are forced to undergo larger magnitudes of lipidomic remodeling in response to temperature when cultivated on lipid diets with a smaller variety of lipid species. We have also demonstrated that larger lipidomes support homeoviscous adaptation in Mycoplasma. Overall, our study showed that varying lipidome size changes the efficiency of membrane lipidome remodeling in response to environmental changes and affects cellular ability to adapt its biophysical properties. At the later stage of my PhD, we have analyzed Mycoplasma transcriptomes to explore protein components responsible for membrane assembly and regulation as a function of membrane lipid composition. The preliminary results identified a non-characterized family of lipoproteins that might be involved in membrane assembly and maintenance in Mycoplasma. Transcriptome experiment opens a roadmap for exploring how lipidome size is linked to cellular metabolism. My PhD work, summarized in this thesis, shows that complex membrane lipidomes are key in supporting membrane biophysical properties and homeostasis. Furthermore, my work sets the stage for the progress in understanding of why living cells evolved to synthesize membrane structures with complex and diverse lipidomes, and what are the minimal requirements for a minimal responsive cell membrane that can support life.

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