Skip to main content

Model of demyelination on a molecular scale at physiological and pathological conditions

Principal investigator

Category
Projekti Hrvatske zaklade za znanost
Project code
UIP-2020-02-7669
Total cost
1.936.000,00
HRK
Start date
Feb 1st 2021
End date
Jan 31st 2026
Status
Active

Description

Myelin is multibilayered, dominantly lipid sheath that enwraps axons and ensures proper transmission of neural impulses. Loss of myelin integrity in terms of redundant unwrapping, vacuole formation and swelling of the bilayer sheaths is referred as demyelination and is related to multiple sclerosis. In vivo studies reported that the amounts of representative lipids, including phosphatidylethanolamines (PEs), are significantly changed in diseased compared to healthy animals, and are further accompanied by reduced adhesive activity of myelin basic protein (MBP). The impact of the amount of PE in mixed model lipid membranes on the transition temperature between lamellar (La) to inverse hexagonal (HII) phase, where the latter shares structural features with vacuole formation, is significant but rather elusive issue. The aim of this proposal is to establish a link between this temperature change and the size and arrangement of PE domains in mixed model lipid membranes in the presence and absence of MBP. Model myelin membranes will be prepared from representative myelin lipids according to their ratios found in normal and diseased species. La to HII phase transitions of PE domains will be studied by probing different surroundings of PE domains within the bilayer, along with the variations in the hydrating medium regarding the presence of MBP and ionic content. A detailed molecular picture of these events will be provided by combining temperature-dependent IR spectroscopy and computational chemistry; structural changes of PE domain during this phase transition will be identified together with the interactions between PE, MBP and neighboring domains. As a result, the parameters considered as the most critical in reduction of La to HII phase transition temperature will be revealed. Aside of understanding demyelination at the molecular level, obtained results will help in suggesting possible solutions in lipid composition regulation by medications and appropriate nutrition.

Papers

7. Pašalić L, Pem B, Bakarić D. Lamellarity-Driven Differences in Surface Structural Features of DPPS Lipids: Spectroscopic, Calorimetric and Computational Study // Membranes, 13 (2023), 83, 22 doi: 10.3390/membranes13010083

6. Ćehić M, Brkljača Z, Filić Ž, Crnolatac I, Vujaklija D, Bakarić D. (Un)coupling the factors contributing to the interfacial activation of Streptomyces rimosus lipase: computational and spectrophotometric study. Journal of dispersion science and technology (2023), in press, doi: 10.1080/01932691.2022.2145304

5. Maleš P, Butumović M, Erceg I, Brkljača Z, Bakarić D. Influence of DPPE surface undulations on melting temperature determination: UV/Vis spectroscopic and MD study. Biochimica et biophysica acta. Biomembranes, 1865 (2023), 1; 184072, 9, doi: 10.1016/j.bbamem.2022.184072

4. Brkljača Z, Butumović M, Bakarić D. Water Does Not Dance as Ions Sing: a New Approach in Elucidation of Ion-Invariant Water Fluctuations. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy, 271 (2022), 120907, 9 doi: 10.1016/j.saa.2022.120907

3. Maleš P, Brkljača Z, Domazet Jurašin D, Bakarić D. New spirit of an old technique: Characterization of lipid phase transitions via UV/Vis spectroscopy. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy, 272 (2022), 121013, 7, doi: 10.1016/j.saa.2022.121013

2. Brkljača Z, Ćehić M, Portada T, Butumović M, Bakarić D, Crnolatac I. Monitoring lipid phase transition temperatures using fluorescent probes and temperature-dependent fluorescence spectroscopy. Dyes and pigments, 206 (2022), 110621, 10, doi: 10.1016/j.dyepig.2022.110621

1. Maleš P, Pem B, Petrov D, Domazet Jurašin D, Bakarić D. Deciphering the origin of the melting profile of unilamellar phosphatidylcholine liposomes by measuring the turbidity of its suspensions. Soft matter, 18 (2022), 6703-6715, doi: 10.1039/D2SM00878E

Theses

2. Munivrana, Jana. Determination of the main phase transition temperature of neutral lipids by UV/Vis spectroscopy, 2022., diploma thesis, Faculty of Science, University of Zagreb

1. Butumović, Marija. Investigation of the influence of ions on the crosslinking of water molecules by FT-IR spectroscopy, 2021., diploma thesis, Faculty of Science, University of Zagreb

Dissemination

11. Bakarić D, Pašalić L, Pem B. Experimental and computational insight into the surface curvature of DPPS lipid bilayers. 16tℎChristmas Biophysics Workshop, Brdo pri Kranju, Slovenia, 2022. str. 16-16 (lecture)

10. Maleš P, Munivrana J, Pašalić L, Bakarić D. The complexity of brain sphingomyelin. Supramolecular Chemistry 22 Book of Abstracts, Frkanec L, Namjesnik D, Tomišić V (ur.). Zagreb: Institut Ruđer Bošković, 2022. str.45-45 (poster)

9. Pem B, Bakarić D. Discerning the Structure and Hydration of Unilamellar and Multilamellar Phosphatidylserine Bilayers Using Molecular Dynamics. Supramolecular Chemistry 2022 Book of Abstracts, Frkanec L, Namjesnik D, Tomišić V (ur.). Zagreb: Institut Ruđer Bošković, 2022. str. 31-31 (poster)

8. Maleš P, Pašalić L, Munivrana J, Bakarić D. Zoom in the brain sphingomyelin. Chemistry towards Biology (CTB10)- Instruct. Bratislava, Slovakia, 2022. (poster)

7. Maleš P, Brkljača Z, Bakarić D. Do the myelin basic protein and phosphatidylcholine lipids like to dance together?. 6. Simpozij studenata doktorskih studija PMF-a. Zagreb, Croatia, 2022. (poster)

6. Maleš P, Brkljača Z, Bakarić D. Love or compulsion relationship between myelin basic protein and phosphatidylcholine lipids. 14. susret mladih kemijskih inženjera (SMLKI). Zagreb, Croatia, 2022. (poster)

5. Bakarić D, Maleš P, Brkljača Z, Butumović M, Erceg I. UV/Vis Spectroscopy in Distinction of Lipid Bilayers Structural Features. 36th European Colloid & Interface Society Conference / Konstantakis G (ur.). Heraklion, Greece: Diazoma Conferences & Events, 2022. str. 280-280 (poster)

4. Pem B, Bakarić D. Molecular Dynamics Study of the Interaction of Guanidinium and Ammonium Cations with Zwitterionic and Anionic Lipid Bilayers. CCD2022-Book of Abstracts. Zagreb: University of Zagreb Faculty of Science, 2022. str. 24-24 (poster)

3. Pem B, Bakarić D. Molecular dynamics study of phosphatidylcholine bilayers with the addition of phosphatidylglycerol. Math/Chem/Comp 2022 and 33rd MC2 Conference : Book of Abstracts, Vančik H, Cioslowski J, Namjesnik D (ur.). Zagreb: Croatian Chemical Society, 2022. str. 33-33 (poster)

2. Bakarić D, Domazet Jurašin D, Brkljača Z, Maleš P. Ion influence on pretransition of multilamellar phosphatidylcholine liposomes. 27. HSKIKI Veli Lošinj, Croatia, 2021. (poster)

1. Brkljača Z, Butumović M, Bakarić D. Are ions reflected in water IR signature?. 11th International Conference on Advanced Vibrational Spectroscopy : Book of Abstracts. Krakow, Poland, 2021. str. 129-129 (lecture)

This site uses cookies.. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and can only be disabled by changing your browser preferences.