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Mechanisms of membrane remodeling induced by amphiphiles and peripheral proteins / Rui Jin.
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Jin, Rui, author.
- Language:
- English
- Subjects (All):
- Chemistry.
- Physiology.
- Cellular biology.
- Plasma.
- Mutation.
- Cholesterol.
- Yeast.
- Lipids.
- Influence.
- Radiation.
- Asymmetry.
- Proteins.
- Membranes.
- Simulation.
- Lipid peroxidation.
- Spectrum analysis.
- Oxidation.
- Experiments.
- Permeability.
- Carbon.
- Kinetics.
- Enzymes.
- Morphology.
- Chemistry--Penn dissertations.
- Penn dissertations--Chemistry.
- Local Subjects:
- Chemistry.
- Physiology.
- Cellular biology.
- Plasma.
- Mutation.
- Cholesterol.
- Yeast.
- Lipids.
- Influence.
- Radiation.
- Asymmetry.
- Proteins.
- Membranes.
- Simulation.
- Lipid peroxidation.
- Spectrum analysis.
- Oxidation.
- Experiments.
- Permeability.
- Carbon.
- Kinetics.
- Enzymes.
- Morphology.
- Chemistry--Penn dissertations.
- Penn dissertations--Chemistry.
- Genre:
- Academic theses.
- Physical Description:
- 1 online resource (257 pages)
- Contained In:
- Dissertations Abstracts International 83-03B.
- Place of Publication:
- [Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2021.
- Language Note:
- English
- System Details:
- Mode of access: World Wide Web.
- text file
- Summary:
- Biological membranes frequently undergo shape changes, which are essential for various cellular processes, including cell signaling, cell trafficking and the function of organelles. Biomembrane remodeling is closely related to the asymmetric distribution of membrane-interacting proteins, lipids, as well as other amphiphiles on the two sides of the membrane bilayer. In this dissertation, we study membrane remodeling induced by asymmetric distribution of oxidized lipids, and the structural stability of a membrane remodeling protein, endophilin, as well as the curvature-dependent interaction between endophilin and a biomimetic membrane. First, we investigated a mechanistic contribution from phospholipids that tend to desorb from the lipid membrane. We observed that giant unilamellar vesicles (GUVs) containing unsaturated phosphatidylinositol-4,5-bisphosphate (PIP2) suffering oxidation tended to show inner tubules upon dilution. Accordingly, the spontaneous curvature of the membrane was measured via tether pulling experiments to be negative. To further look into the impact of lipid oxidation, we focused on two lipid oxidation products, 1-oleoyl-2-hydroxy-sn-glycero-3-phosphocholine (18:1 LysoPC), and 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PAzePC). According to kinetic measurements via a microfluidic approach, the rate of transmembrane movement of the two lipids was found to be 10- to 100- fold lower compared to their desorption rate. Thus, membrane asymmetry can be induced and maintained after asymmetric lipid desorption. Such lipid distribution asymmetry was proved to induce membrane remodeling such as increased tubules on GUVs containing only 2 % PAzePC or LysoPC. Secondly, we investigated the mechanism of the interaction between biomimetic membranes and an N-BAR protein, endophilin. We first looked into the thermal stability of the dimerized N-BAR domain (endo_N-BAR) since this curved domain directly interacts with bio-membranes and can bend the membrane via a scaffolding mechanism. A two-step thermal unfolding mechanism was proposed based on both the conformation and helicity changes of endophilin: The tip region unfolds first while the dimerization interface is more stable. We also found that the presence of the flexible linker and H0 enhanced the thermal stability of endophilin, which may contribute to the rigidity of the dimeric BAR domain upon its membrane interaction. Next, we investigated the interaction of endophilin N-BAR with mimetic biomembranes and its curvature dependence. We found that the unbinding rate of endo_N-BAR decreased with increased membrane curvature, which supports the hypothesis that endophilin can be recruited by a high membrane curvature to participate in membrane remodeling in vivo such as endocytosis.
- Notes:
- Source: Dissertations Abstracts International, Volume: 83-03, Section: B.
- Advisors: Baumgart, Tobias; Committee members: Feng, Gai; Saven, Jeffery G.; Ostap, Michael.
- Department: Chemistry.
- Ph.D. University of Pennsylvania 2021.
- Local Notes:
- School code: 0175
- ISBN:
- 9798535590110
- Access Restriction:
- Restricted for use by site license.
- This item is not available from ProQuest Dissertations & Theses.
- This item must not be sold to any third party vendors.
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