Prijeđite na glavni sadržaj
Kategorija
Projekti Hrvatske zaklade za znanost
Iznos financiranja
256.951,36
EUR
Datum početka
1.2.2021.
Datum završetka
31.1.2026.
Status
Aktivan

Glavni istraživač

Sažetak

Mijelin je višestruko-dvoslojna, pretežno lipidna ovojnica koja omata aksone i osigurava pravilan prijenos živčanih impulsa. Gubitak cjelovitosti mijelina u obliku njegovog prekomjernog odmotavanja, stvaranja vakuola te bubrenja dvosloja naziva se demijelinizacijom koja je povezana s multiplom sklerozom (MS). In vivo studije provedene na oboljelim životinjama pokazale su da su količine najzastupljenijih lipida, uključujući fosfatidiletanolamine (PE), značajno promijenjene u usporedbi sa zdravima, a prati ih i smanjena adhezivna aktivnost mijelin-bazičnog proteina (MBP). Utjecaj povećanja PE u mješovitim modelnim lipidnim membranama na temperaturu faznog prijelaza iz lamelarne (La) u inverznu heksagonsku (HII) fazu, koji pokazuje strukturne sličnosti s formiranjem vakuola, značajan je, ali prilično nedokučiv problem. Cilj ovog prijedloga je naći vezu između spomenute temperaturne promjene te veličine i rasporeda PE-domena u mješovitim modelnim lipidnim membranama uz i bez prisustva MBP-a. Modelne mijelinske membrane priredit će se iz najzastupljenijih mijelinskih lipida u skladu s njihovim omjerima u normalnim i oboljelim jedinkama. Uz različito okruženje PE domena unutar dvosloja, zajedno s promjenama u hidratacijskom mediju u pogledu prisustva MBP-a te ionskog sadržaja, sustavno će se proučiti promjene temperature La do HII faznog prijelaza PE domena. Detaljna molekularna slika tih događaja dobit će se kombinacijom temperaturno-ovisne IR spektroskopije i računalne kemije; strukturne promjene PE domena tijekom ove fazne promjene otkrit će se zajedno s interakcijama između PE, MBP i susjednih domena. Odredit će se parametri koji se smatraju najkritičnijima u smanjenju temperature faznog prijelaza La do HII. Osim razumijevanja demijelinizacije na molekularnoj razini, dobiveni rezultati će također pomoći u predlaganju mogućih rješenja u regulaciji lipidnog sastava lijekovima te odgovarajućom prehranom.

Publikacije

20. Maleš P, Munivrana J, Pašalić L, Pem B, Bakarić D. Reorientation of interfacial water molecules during melting of brain sphingomyelin is associated with the phase transition of its C24:1 sphingomyelin lipids // Chemistry and physics of lipids, 264 (2024), 105434, 10. doi: 10.1016/j.chemphyslip.2024.105434

19. Pem B, Liu Q, Pašalić L, Edely M, Lamy de la Chapelle Marc, Bakarić D. Uncoated gold nanoparticles create fewer and less localized defects in model prokaryotic than in model eukaryotic lipid membranes // Colloids and surfaces. B, Biointerfaces, 243 (2024), 114158, 13. doi: 10.1016/j.colsurfb.2024.114158
18. Pem B, Vazdar M, Bakarić D. Elucidation of the hydration pattern of trifluoroacetic acid in dilute solutions: FTIR and computational study // Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy, 323 (2024), 124900, 7. doi: 10.1016/j.saa.2024.124900

17. Pem B, Pišonić M, Momčilov M, Crnolatac I, Brkljača Z, Vazdar M, Bakarić D. Protonation of palmitic acid embedded in DPPC lipid bilayers obscures detection of ripple phase by FTIR spectroscopy // Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy, 322 (2024), 124773, 11. doi: 10.1016/j.saa.2024.124773

16. Maleš P, Nikšić-Franjić I, Wang A, Pem B, Bakarić D. Optical and molecular features of negatively curved surfaces created by POPE lipids: A crucial role of the initial conditions // Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy, 317 (2024), 124462, 12. doi: 10.1016/j.saa.2024.124462

15. Pavlek AM, Pem B, Bakarić D. The Signature of Fluctuations of the Hydrogen Bond Network Formed by Water Molecules in the Interfacial Layer of Anionic Lipids // Biophysica, 4 (2024), 1; 92-106. doi: 10.3390/biophysica4010007

14. Maleš P, Brkljača Z, Crnolatac I, Petrov D, Bakarić D. Phase-Dependent Adsorption of Myelin Basic Protein to Phosphatidylcholine Lipid Bilayers // Membranes, 14 (2024), 1; 15, 20. doi: https://doi.org/10.3390/membranes14010015

13. Pašalić L, Maleš P, Čikoš A, Pem B, Bakarić D. The rise of FTIR spectroscopy in the characterization of asymmetric lipid membranes // Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy (2024), 123488, 13, doi: 10.1016/j.saa.2023.123488

12. Pašalić L, Jakas A, Pem B, Bakarić D. Adsorption/Desorption of Cationic-Hydrophobic Peptides on Zwitterionic Lipid Bilayer Is Associated with the Possibility of Proton Transfer // Antibiotics (2023) 12, 1216, doi: 10.3390/antibiotics12071216

11. Pem B, Brkljača Z, Philippe A, Schaumann GE, Vazdar M, Bakarić D. FTIR spectroscopy and molecular level insight of diluted aqueous solutions of acetic acid // Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy (2023) 123135, 10, doi: 10.1016/j.saa.2023.123135

10. Pašalić L, Liu Q, Vukosav P, Mišić Radić T, Azziz A, Majdinasab M, Edely M, Lamy de la Chapelle M, Bakarić D. The presence of uncoated gold nanoparticle aggregates may alter the phase of phosphatidylcholine lipid as evidenced by vibrational spectroscopies // Journal of Liposome Research (2023) doi: 10.1080/08982104.2023.2239905

9. Pašalić L, Pem B, Domazet Jurašin D, Vazdar M, Bakarić D. Interaction of guanidinium and ammonium cations with phosphatidylcholine and phosphatidylserine lipid bilayers – Calorimetric, spectroscopic and molecular dynamics simulations study // Biochimica et Biophysica Acta - Biomembranes (2023) doi: 10.1016/j.bbamem.2023.184122

8. Vukosav P, Pašalić L, Bakarić D, Domazet Jurašin D, Mišić Radić T. Interaction of Silica Nanoparticles with Microalgal Extracellular Polymers // Water, 15 (2023), 3; 159-159 doi: 10.3390/w15030519

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

Ocjenski radovi

2. Munivrana, Jana. Određivanje temperature glavnog faznog prijelaza neutralnih lipida UV/Vis spektroskopijom, 2022., diplomski rad, Prirodoslovno-matematički fakultet, Zagreb

1. Butumović, Marija. Istraživanje utjecaja iona na umreženost molekula vode FT-IR spektroskopijom, 2021., diplomski rad, Prirodoslovno-matematički fakultet, Zagreb

Diseminacija

26. Maleš P, Bakarić D. The significance of cholesterol for myelin lipid phases // XV Meeting Of Young Chemical Engineers - Book Of Abstracts / XV. susret mladih kemijskih inženjera - knjiga sažetaka. Zagreb: Hrvatsko društvo kemijskih inženjera i tehnologa (HDKI), 2024. str. 26-26 (poster)

25. Pašalić L, Mangiarotti A, Jakas A, Bakarić D. Potential cell penetrating peptides in interaction with lipid bilayers // 7th Mini Symposium of Section of Medicinal and Pharmaceutical Chemistry: Book of Abstracts. Zagreb: HKD - sekcija za medicinsku i farmaceutsku kemiju, 2023. str. 3.-3 (poster)

24. Maleš P, Bakarić D. The revelation of interactions in model myelin with FTIR spectroscopy // ICAVS12: International Conference on Advanced Vibrational Spectroscopy, Krakow, Poljska, 2023. str. 283-283. (poster)

23. Pem B, Pašalić L, Bakarić D. Lipid interactions with different cationic peptides: towards the understanding of membrane disrupting activity // IX EFMC International Symposium on Advances in Synthetic and Medicinal Chemistry, Zagreb, Hrvatska, 2023. str. 278-278. (poster)

22. Maleš P, Mangiarotti A, Bakarić D. What to Say about the Structural Integrity of Myelin? // Peptide Chemistry Day, Zagreb, Hrvatska, 2023. str. 25-25. (poster)
21. Pašalić L, Jakas A, Mangiarotti A, Bakarić D. Influence of cationic peptides on the properties of unilamellar phosphatidylcholine vesicles // Peptide chemistry day 2023 : Book of abstracts. Zagreb: Hrvatsko kemijsko društvo; Sveučilište u Zagrebu, 2023. str. 15.-15 (poster)   
20. Pem B, Bakarić D. Molecular Dynamics Study of  Cationic Peptide Adsorption on Zwitterionic Lipid Bilayers // Peptide chemistry day 2023 : Book of abstracts. Zagreb: Hrvatsko kemijsko društvo; University of Zagreb, 2023. str. 24-24 (poster)

19. Pem B, Bakarić D. Structural Differences of Symmetric and Asymmetric Mixed-Lipid Bilayers Observed by Classical Molecular Dynamics // Computational Chemistry Day 2023, Zagreb, Hrvatska, 2023. str. 25-25. (poster)

18. Bakarić D, Pašalić L, Maleš P, Pem B, Čikoš A. Synergy of NMR and FTIR spectroscopy in the characterization of asymmetric liposomes // 7th Adriatic NMR Conference, Mali Ston, Hrvatska, 2023. str. 41-41 (predavanje)

17. Pašalić L, Bakarić D, Jakas A. Arginine-rich peptides vs. Lysine-rich peptides: impact on differently charged lipid bilayers // 7th Faculty of Science PhD Student Symposium, Zagreb, Hrvatska, 2023. str. 51-51 (predavanje)

16. Maleš P, Bakarić D. The signature of inverse hexagonal phase of phosphoethanolamine lipids // 28HSKIKI, Rovinj, Hrvatska, 2023. str. 98-98 (poster)

15. Pašalić L, Bakarić D, Liu Q, Lamy de la Chapelle M. Physical-chemical properties of DPPC liposomes in the presence of gold nanoparticles aggregates 28HSKIKI, Rovinj, Hrvatska, 2023. str. 112-112 (poster)

14. Pašalić L, Bakarić D. Thermotropic properties of unilamellar and multilamellar DPPS bilayers. Supramolecular Chemistry 2022, Zagreb, Hrvatska, 2022. str. 32-32 (poster)

13. Pašalić L, Bakarić D. Utjecaj NH4+ i Gdm+ kationa na termička svojstva DPPS lipidnih membrana. 6th Faculty of Science PhD Student Symposium, Zagreb, Hrvatska, 2022. str. 148-149 (poster)

12. Pašalić L, Bakarić D. Impact of different cations on thermal properties of DPPS and DPPC bilayers. European Student Colloid Conference, Szeged, Mađarska, 2022. str. 92-92 (poster)

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, Slovenija, 2022. str. 16-16 (predavanje)

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, Slovačka, 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, Hrvatska, 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, Hrvatska, 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, Grčka: 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, Hrvatska, 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, Poljska, 2021. str. 129-129 (predavanje)

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