Structural changes in fasted state dietary mixed micelles upon solubilization of beta-carotene

Year 2022, , 480 - 493, 23.09.2022

Beste Bayramoğlu

https://doi.org/10.31015/jaefs.2022.3.18

Abstract

It was aimed to investigate the structural changes taking place in duodenal mixed micelles (MM) at fasted state with the incorporation of fatty acids (FA) and the morphological transformations in these MMs upon solubilization of β-carotene (BCR) through coarse-grained (CG) molecular dynamics (MD) simulations. All simulations were performed with GROMACS 2019 simulation package using the Martini force field. Lauric acid (LA), stearic acid (SA) and linoleic acid (LNA) were used to explore the effects of FA chain length and unsaturation. Micelle swelling was observed with the incorporation of all FAs. The increase in size was in line with increasing FA chain length and unsaturation. MMs incorporating LA and SA were ellipsoidal in shape, while polyunsaturated LNA resulted in a worm-like MM. Upon solubilization of BCRs, swelling was observed only in the MMs with long-chain SA and LNA. No micelle growth was observed in the plain and LA MMs despite their smaller sizes. This was attributed to their low-density hydrophobic cores, which allowed a condensation effect induced by the interactions between BCRs and POPC tails. It is inferred that when the micelle is large enough to solubilize BCRs, whether or not swelling will take place depends on the core density. The increase in micelle size was very small in the MM incorporating LNA compared to that in the MM with SA, which was accompanied by an elliptical-to-cylindrical shape transformation. This was due to the fluid nature of the worm-like LNA micelle, which readily allowed the solubilization of 3 BCRs within its core. By resolving the internal structures of BCR incorporated MMs, this study gives valuable insight into the effects of FA chain length and unsaturation on the solubilization behavior of dietary MMs. The results are expected to give direction to the development of rational design strategies for effective BCR delivery systems.

Keywords

Molecular dynamics simulation, β-carotene, dietary mixed micelle, bioaccessibility, nutraceutical delivery system

Supporting Institution

TÜBİTAK

Project Number

118O378

Thanks

This study was supported by The Scientific and Technological Research Council of Turkey (TUBITAK) (grant number:118O378). Computing sources were provided by the National Center for High Performance Computing of Turkey (UHEM) under grant number 5004012016.

References

• Abraham, M.J., Murtola, T., Schulz, R., Páll, S., Smith, J.C., Hess, B., Lindah, E. (2015). Gromacs: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1–2, 19–25. https://doi.org/10.1016/j.softx.2015.06.001
• Berendsen, H.J.C., Postma, J.P.M., Gunsteren, W.F. Van, Dinola, A., Haak, J.R. (1984). Molecular dynamics with coupling to an external bath. J. Chem. Phys. 3684. https://doi.org/10.1063/1.448118
• Birru, W.A., Warren, D.B., Ibrahim, A., Williams, H.D., Benameur, H., Porter, C.J.H., Chalmers, D.K., Pouton, C.W. (2014). Digestion of phospholipids after secretion of bile into the duodenum changes the phase behavior of bile components. Mol. Pharm. 11, 2825–2834. https://doi.org/10.1021/mp500193g
• Bogusz, S., Venable, R.M., Pastor, R.W. (2000). Molecular Dynamics Simulations of Octyl Glucoside Micelles: Structural Properties. J. Phys. Chem. B 104, 5462–5470. https://doi.org/10.1021/jp000159y
• Bustos, A.Y., Raya, R., de Valdez, G.F., Taranto, M.P. (2011). Efflux of bile acids in Lactobacillus reuteri is mediated by ATP. Biotechnol. Lett. 33, 2265–2269. https://doi.org/10.1007/s10529-011-0696-3
• Cheng, X., Jo, S., Lee, H.S., Klauda, J.B., Im, W. (2013). CHARMM-GUI micelle builder for pure/mixed micelle and protein/micelle complex systems. J. Chem. Inf. Model. https://doi.org/10.1021/ci4002684
• Clulow, A.J., Parrow, A., Hawley, A., Khan, J., Pham, A.C., Larsson, P., Bergström, C.A.S., Boyd, B.J. (2017). Characterization of Solubilizing Nanoaggregates Present in Different Versions of Simulated Intestinal Fluid. J. Phys. Chem. B 121, 10869–10881. https://doi.org/10.1021/acs.jpcb.7b08622
• Cohen, D.E., Thurston, G.M., Chamberlin, R.A., Benedek, G.B., Carey, M.C. (1998). Laser light scattering evidence for a common wormlike growth structure of mixed micelles in bile salt- and straight-chain detergent- phosphatidylcholine aqueous systems: Relevance to the micellar structure of bile. Biochemistry 37, 14798–14814. https://doi.org/10.1021/bi980182y
• de Jong, D.H., Liguori, N., van den Berg, T., Arnarez, C., Periole, X., Marrink, S.J. (2015). Atomistic and Coarse Grain Topologies for the Cofactors Associated with the Photosystem II Core Complex. J. Phys. Chem. B 119, 7791–7803. https://doi.org/10.1021/acs.jpcb.5b00809
• El Aoud, A., Reboul, E., Dupont, A., Mériadec, C., Artzner, F., Marze, S. (2021). In vitro solubilization of fat-soluble vitamins in structurally defined mixed intestinal assemblies. J. Colloid Interface Sci. 589, 229–241. https://doi.org/10.1016/j.jcis.2021.01.002
• Fatouros, D.G., Bergenstahl, B., Mullertz, A. (2007). Morphological observations on a lipid-based drug delivery system during in vitro digestion. Eur. J. Pharm. Sci. 31, 85–94. https://doi.org/10.1016/j.ejps.2007.02.009
• Fatouros, D.G., Walrand, I., Bergenstahl, B., Mullertz, A. (2009). Physicochemical characterization of simulated intestinal fed-state fluids containing lyso-phosphatidylcholine and cholesterol. Dissolution Technol. 16, 47–50. https://doi.org/10.14227/DT160309P47
• Gleize, B., Tourniaire, F., Depezay, L., Bott, R., Nowicki, M., Albino, L., Lairon, D., Kesse-Guyot, E., Galan, P., Hercberg, S., Borel, P. (2013). Effect of type of TAG fatty acids on lutein and zeaxanthin bioavailability. Br. J. Nutr. 110, 1–10. https://doi.org/10.1017/S0007114512004813
• Hess, B., Bekker, H., Berendsen, H.J.C., Fraaije, J.G.E.M. (1997). LINCS: A linear constraint solver for molecular simulations. J. Comput. Chem. 18, 1463–1472. https://doi.org/10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H
• Hjelm, R.P., Alkan, M.H., Thiyagarajan, P. (1990). Small-Angle Neutron Scattering Studies of Mixed Bile Salt-Lecithin Colloids. Mol. Cryst. Liq. Cryst. Inc. Nonlinear Opt. 180, 155–164. https://doi.org/10.1080/00268949008025796
• Hjelm, R.P., Thiyagarajan, P., Önyüksel, H. (1992). Organization of phosphatidylcholine and bile salt in rodlike mixed micelles. J. Phyical Chem. 96, 8653–8661. https://doi.org/10.1021/j100200a080
• Humphrey, W., Dalke, A., Schulten, K. (1996). VMD: Visual molecular dynamics. J. Mol. Graph. 14, 33–38. https://doi.org/10.1016/0263-7855(96)00018-5
• Huo, T., Ferruzzi, M.G., Schwartz, S.J., Failla, M.L. (2007). Impact of fatty acyl composition and quantity of triglycerides on bioaccessibility of dietary carotenoids. J. Agric. Food Chem. 55, 8950–8957. https://doi.org/10.1021/jf071687a
• Jemioła-Rzemińska, M., Pasenkiewicz-Gierula, M., Strzałka, K. (2005). The behaviour of β-carotene in the phosphatidylcholine bilayer as revealed by a molecular simulation study. Chem. Phys. Lipids 135, 27–37. https://doi.org/10.1016/j.chemphyslip.2005.01.006
• Jójárt, B., Poša, M., Fiser, B., Szori, M., Farkaš, Z., Viskolcz, B. (2014). Mixed micelles of sodium cholate and sodium dodecylsulphate 1:1 binary mixture at different temperatures - Experimental and theoretical investigations. PLoS One 9, 1–9. https://doi.org/10.1371/journal.pone.0102114
• Khoshakhlagh, P., Johnson, R., Nawroth, T., Langguth, P., Schmueser, L., Hellmann, N., Decker, H., Szekely, N.K. (2014). Nanoparticle structure development in the gastro-intestinal model fluid FaSSIF mod6.5 from several phospholipids at various water content relevant for oral drug administration. Eur. J. Lipid Sci. Technol. 116, 1155–1166. https://doi.org/10.1002/ejlt.201400066
• Kossena, G.A., Boyd, B.J., Porter, C.J.H., Charman, W.N. (2003). Separation and characterization of the colloidal phases produced on digestion of common formulation lipids and assessment of their impact on the apparent solubility of selected poorly water-soluble drugs. J. Pharm. Sci. 92, 634–648. https://doi.org/10.1002/jps.10329
• Madenci, D., Salonen, A., Schurtenberger, P., Pedersen, J.S., Egelhaaf, S.U. (2011). Simple model for the growth behaviour of mixed lecithin-bile salt micelles. Phys. Chem. Chem. Phys. 13, 3171–3178. https://doi.org/10.1039/c0cp01700k
• Marrink, S. J. (2004). Molecular dynamics simulation of cholesterol nucleation in mixed micelles modelling human bile. In G. Adler, M. Fuchs, HE. Blum, & EF. Stange (Eds.), GALLSTONES: PATHOGENESIS AND TREATMENT (pp. 98-105 - 13). (FALK SYMPOSIUM; Vol. 139). Kluwer Academic Publishers.
• Marrink, S.J., Mark, A.E. (2002). Molecular Dynamics Simulations of Mixed Micelles Modeling Human Bile. Biochemistry 41, 17, 5375–5382. https://doi.org/10.1021/bi015613i
• Marrink, S.J., Risselada, H.J., Yefimov, S., Tieleman, D.P., De Vries, A.H. (2007). The MARTINI force field: Coarse grained model for biomolecular simulations. J. Phys. Chem. B 111, 7812–7824. https://doi.org/10.1021/jp071097f
• Marrink, S.J., Tieleman, D.P. (2013). Perspective on the Martini model. Chem. Soc. Rev. 42, 6801. https://doi.org/10.1039/c3cs60093a
• Martini General Purpose Coarse-Grained Force Field (2022, August 10). Force field parameters. Retrieved from http://cgmartini.nl/index.php/force-field-parameters
• Mashurabad, P.C., Palika, R., Jyrwa, Y.W., Bhaskarachary, K., Pullakhandam, R. (2017). Dietary fat composition, food matrix and relative polarity modulate the micellarization and intestinal uptake of carotenoids from vegetables and fruits. J. Food Sci. Technol. 54, 333–341. https://doi.org/10.1007/s13197-016-2466-7
• Matsuoka, K., Maeda, M., Moroi, Y. (2004). Characteristics of conjugate bile salt–phosphatidylcholine–cholesterol–water systems. Colloids Surfaces B Biointerfaces 33, 101–109. https://doi.org/10.1016/j.colsurfb.2003.09.002
• Mazer, N.A., Benedek, G.B., Carey, M.C. (1980). Quasielastic Light-Scattering Studies of Aqueous Biliary Lipid Systems. Mixed Micelle Formation in Bile Salt-Lecithin Solutions. Biochemistry 19, 601–615. https://doi.org/10.1021/bi00545a001
• Mostofian, B., Johnson, Q.R., Smith, J.C., Cheng, X. (2020). Carotenoids promote lateral packing and condensation of lipid membranes. Phys. Chem. Chem. Phys. 22, 12281–12293. https://doi.org/10.1039/D0CP01031F
• Nagao, A., Kotake-Nara, E., Hase, M. (2013). Effects of fats and oils on the bioaccessibility of carotenoids and vitamin E in vegetables. Biosci. Biotechnol. Biochem. 77, 1055–60. https://doi.org/10.1271/bbb.130025
• Parrow, A., Larsson, P., Augustijns, P., Bergström, C.A.S. (2020). Molecular Dynamics Simulations on Interindividual Variability of Intestinal Fluids: Impact on Drug Solubilization. Mol. Pharm. 17, 3837–3844. https://doi.org/10.1021/acs.molpharmaceut.0c00588
• Phan, S., Salentinig, S., Gilbert, E., Darwish, T.A., Hawley, A., Nixon-Luke, R., Bryant, G., Boyd, B.J. (2015). Disposition and crystallization of saturated fatty acid in mixed micelles of relevance to lipid digestion. J. Colloid Interface Sci. 449, 160–166. https://doi.org/10.1016/j.jcis.2014.11.026
• Qian, C., Decker, E.A., Xiao, H., McClements, D.J. (2012). Nanoemulsion delivery systems: Influence of carrier oil on β-carotene bioaccessibility. Food Chem. 135, 1440–1447. https://doi.org/10.1016/j.foodchem.2012.06.047
• Sayyed-Ahmad, A., Lichtenberger, L.M., Gorfe, A.A. (2010). Structure and dynamics of cholic acid and dodecylphosphocholine-cholic acid aggregates. Langmuir 26, 13407–13414. https://doi.org/10.1021/la102106t
• Schurtenberger, P., Mazer, N., Känzig, W. (1985). Micelle to vesicle transition in aqueous solutions of bile salt and lecithin. J. Phys. Chem. 89, 1042–1049. https://doi.org/10.1021/j100252a031
• Suys, E.J.A., Warren, D.B., Porter, C.J.H., Benameur, H., Pouton, C.W., Chalmers, D.K. (2017). Computational Models of the Intestinal Environment. 3. the Impact of Cholesterol Content and pH on Mixed Micelle Colloids. Mol. Pharm. 14, 3684–3697. https://doi.org/10.1021/acs.molpharmaceut.7b00446
• Tande, B.M., Wagner, N.J., Mackay, M.E., Hawker, C.J., Jeong, M. (2001). Viscosimetric, hydrodynamic, and conformational properties of dendrimers and dendrons. Macromolecules 34, 8580–8585. https://doi.org/10.1021/ma011265g
• Tuncer, E., Bayramoglu, B. (2019). Characterization of the self-assembly and size dependent structural properties of dietary mixed micelles by molecular dynamics simulations. Biophys. Chem. 248, 16–27. https://doi.org/10.1016/j.bpc.2019.02.001
• Tunçer, E., Bayramoğlu, B. (2022). Molecular dynamics simulations of duodenal self assembly in the presence of different fatty acids. Colloids Surfaces A Physicochem. Eng. Asp. 644. https://doi.org/10.1016/j.colsurfa.2022.128866
• Van Der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A.E., Berendsen, H.J.C. (2005). GROMACS: Fast, flexible, and free. J. Comput. Chem. 26, 1701–1718. https://doi.org/10.1002/jcc.20291
• Wilson, M.D., Rudel, L.L. (1994). Review of cholesterol absorption with emphasis on dietary and biliary cholesterol. J. Lipid Res. 35, 943–955. https://doi.org/10.1016/S0022-2275(20)40109-9
• Wright, A.J., Pietrangelo, C., MacNaughton, A. (2008). Influence of simulated upper intestinal parameters on the efficiency of beta carotene micellarisation using an in vitro model of digestion. Food Chem. 107, 1253–1260. https://doi.org/10.1016/j.foodchem.2007.09.063
• Yao, K., Mcclements, D.J., Xiao, H., Liu, X. (2019). Improvement of carotenoid bioaccessibility from spinach by co-ingesting with excipient nanoemulsions: impact of the oil phase composition. Food Funct. 10, 5302–5311. https://doi.org/10.1039/c9fo01328h
• Yuan, X., Liu, X., Mcclements, D.J., Cao, Y., Xiao, H. (2018). Enhancement of phytochemical bioaccessibility from plant-based foods using excipient emulsions : impact of lipid type on carotenoid solubilization. Food Funct. 9, 4352–4365. https://doi.org/10.1039/c8fo01118d