Thermodynamic and Structural Properties of Biomimetic Monolayers Containing Cholesterol and Magnetite Nanoparticles
Abstract
The thermodynamic and structural properties of biomimetic monolayers composed of cholesterol, dipalmitoylphosphatidylcholine, and hydrophobic magnetite (Fe₃O₄) nanoparticles were investigated under varying cholesterol molar fractions and pH conditions (4.8 and 7.4). Langmuir monolayer experiments were performed to analyze surface pressure-area isotherms, excess molecular area, excess Gibbs free energy of mixing, and compressibility modulus to assess lipid monolayer phase behavior, molecular organization, and mechanical stability. The results confirm that cholesterol enhances monolayer condensation up to a cholesterol molar fraction of 0.50, particularly at pH 7.4, where stronger lipid-lipid interactions promote molecular ordering and increase monolayer rigidity. At cholesterol molar fractions of 0.75 and higher, steric hindrance and phase separation effects emerge, disrupting monolayer homogeneity. pH significantly influences monolayer stability, with pH 7.4 favoring lipid condensation, whereas pH 4.8 induces monolayer expansion and molecular disorder. Excess molecular area and Gibbs free energy of mixing analyses indicate the strongest cholesterol-lipid interactions at a cholesterol molar fraction of 0.25 for pH 4.8 and 0.50 for pH 7.4, confirming these compositions as the most thermodynamically stable. Compressibility modulus analysis demonstrates that cholesterol enhances monolayer rigidity, with pH 7.4 producing higher values. However, at high cholesterol molar fractions, compressibility modules slightly decrease, suggesting steric constraints and lateral phase separation. The incorporation of magnetite nanoparticles increases molecular area and slightly reduces monolayer rigidity at low cholesterol molar fractions due to steric disruptions, but at cholesterol molar fractions of 0.50 and higher, cholesterol stabilizes the monolayer, counteracting nanoparticle-induced perturbations. These findings provide insight into the thermodynamic and structural regulation of biomimetic lipid monolayers by cholesterol and magnetite nanoparticles, with implications for nanomedicine, membrane biophysics, and lipid-based nanostructures.
Keywords
Cholesterol Dipalmitoylphosphatidylcholine Hydrophobic Magnetite nanoparticles Monolayer stability Surface pressure Phase behavior
Ethical Statement
Ethics committee approval was not required for this study because of there was no study on animals or humans.
References
- Bodik M, Jergel M, Majkova E, Siffalovic P. 2020. Langmuir films of low-dimensional nanomaterials. Adv Colloid Interface Sci, 283: 102239.
- Cullis PR, Hope MJ, Bally MB, Madden TD, Mayer LD, Fenske DB. 1997. Influence of pH gradients on the transbilayer transport of drugs, lipids, peptides, and metal ions into large unilamellar vesicles. Biochim Biophys Acta, 1331: 187-211.
- Dana RM. 1999. The monolayer technique: a potent tool for studying the interfacial properties of antimicrobial and membrane-lytic peptides and their interactions with lipid membranes. Biochim Biophys Acta, 1462: 109-140.
- Ding C, Tong L, Feng J, Fu J. 2016. Recent advances in stimuli-responsive release function drug delivery systems for tumor treatment. Molecules, 21: 1715.
- Ganta S, Devalapally H, Shahiwala A, Amiji M. 2008. A review of stimuli-responsive nanocarriers for drug and gene delivery. J Control Release, 126(3): 187-204.
- Gao W, Chan JM, Farokhzad OC. 2010. pH-responsive nanoparticles for drug delivery. Mol Pharm, 7(6): 1913-20.
- Gong K, Feng SS, Go ML, Soew PH. 2002. Effects of pH on the stability and compressibility of DPPC/cholesterol monolayers at the air-water interface. Colloids Surf. A: Physicochem. Eng Asp, 207: 113-125.
- Hao C, Li J, Mu W, Zhu L, Yang J, Liu T, Li B, Chen S, Sun R. 2016. Adsorption behavior of magnetite nanoparticles into the DPPC model membranes. Appl Surf Sci, 362: 121-125.
- He H, Sun R, Hao C, Yang J, Wang M, Zhang L. 2014. Thermodynamic analysis and AFM study of the interaction of palmitic acid with DPPE in Langmuir monolayers. Colloids Surf. A: Physicochem Eng Asp, 441: 184-194.
- Jurak M. 2013. Thermodynamic aspects of cholesterol effect on properties of phospholipid monolayers: Langmuir and Langmuir−Blodgett monolayer study. J Phys Chem B, 117(12): 3496-3502.
- Jurak M, Mroczka R, Łopucki R. 2018. Properties of artificial phospholipid membranes containing lauryl gallate or cholesterol. J Membr Biol, 251: 277-294.
- Marsh D. 1996. Lateral pressure in membranes. Biochim. Biophys Acta, 1286: 183-223.
- Moya Betancourt SN, Cámara CI, Riva JS. 2023. Interaction between pharmaceutical drugs and polymer-coated Fe3O4 magnetic nanoparticles with Langmuir monolayers as cellular membrane models. Pharmaceutics, 15: 311.
- Oliveira ON Jr, Caseli L, Ariga K. 2022. The past and the future of Langmuir and Langmuir-Blodgett films. Chem Rev, 122: 6459-6513.
- Peetla C, Jin S, Weimer J, Elegbede A, Labhasetwar V. 2014. Biomechanics and thermodynamics of nanoparticle interactions with plasma and endosomal membrane lipids in cellular uptake and endosomal escape. Langmuir, 30: 7522-7532.
- Piosik E, Ziegler-Borowska M, Chełminiak-Dudkiewicz D, Martyński T. 2021. Effect of aminated chitosan-coated Fe3O4 nanoparticles with applicational potential in nanomedicine on DPPG, DSPC, and POPC Langmuir monolayers as cell membrane models. Int J Mol Sci, 22: 2467.
- Rosilio V. 2017. How can artificial lipid models mimic the complexity of molecule-membrane interactions? Adv. Biomembr. Lipid Self-Assembly, 27: 107-141.
- Salas SD, Villanueva ME, Selzer SM, Ferreyra NF, Vico RV. 2024. A systematic study of the impact of aromatic/aliphatic amines and protein corona as coatings of iron oxide magnetic nanoparticles on the interaction with DPPC Langmuir monolayers. Surf Interfaces, 51: 104771.
- Swierczewski M, Bürgi T. 2023. Langmuir and Langmuir−Blodgett films of gold and silver nanoparticles. Langmuir, 39: 2135−2151.
- Szcześ A, Jurak M, Chibowski E. 2012. Stability of binary model membranes—Prediction of the liposome stability by the Langmuir monolayer study. J Colloid Interface Sci, 372: 212-216.
- Torrano AA, Pereira ÂS, Oliveira Jr ON, Barros-Timmons A. 2013. Probing the interaction of oppositely charged gold nanoparticles with DPPG and DPPC Langmuir monolayers as cell membrane models. Colloids Surf B: Biointerfaces, 108: 120-126.
- Vázquez-González ML, Botet-Carreras A, Domènech Ò, Montero TM, Borrell JH. 2019. Planar lipid bilayers formed from thermodynamically-optimized liposomes as new featured carriers for drug delivery systems through human skin. Int J Pharm, 563: 1-8.
- Wrobel EC, Guimarães IDL, Wohnrath K, Oliveira ON Jr. 2024. Effects induced by η⁶-ᴘ-cymene ruthenium(II) complexes on Langmuir monolayers mimicking cancer and healthy cell membranes do not correlate with their toxicity. Biochim Biophys Acta Biomembr, 1866: 184332.
- Zhang W, Wang F, Wang Y, Wang J, Yu Y, Guo S, Chen R, Zhou D. 2016. pH and near-infrared light dual-stimuli responsive drug delivery using DNA-conjugated gold nanorods for effective treatment of multidrug resistant cancer cells. J Control Release, 82: 204.
Thermodynamic and Structural Properties of Biomimetic Monolayers Containing Cholesterol and Magnetite Nanoparticles
Abstract
The thermodynamic and structural properties of biomimetic monolayers composed of cholesterol, dipalmitoylphosphatidylcholine, and hydrophobic magnetite (Fe₃O₄) nanoparticles were investigated under varying cholesterol molar fractions and pH conditions (4.8 and 7.4). Langmuir monolayer experiments were performed to analyze surface pressure-area isotherms, excess molecular area, excess Gibbs free energy of mixing, and compressibility modulus to assess lipid monolayer phase behavior, molecular organization, and mechanical stability. The results confirm that cholesterol enhances monolayer condensation up to a cholesterol molar fraction of 0.50, particularly at pH 7.4, where stronger lipid-lipid interactions promote molecular ordering and increase monolayer rigidity. At cholesterol molar fractions of 0.75 and higher, steric hindrance and phase separation effects emerge, disrupting monolayer homogeneity. pH significantly influences monolayer stability, with pH 7.4 favoring lipid condensation, whereas pH 4.8 induces monolayer expansion and molecular disorder. Excess molecular area and Gibbs free energy of mixing analyses indicate the strongest cholesterol-lipid interactions at a cholesterol molar fraction of 0.25 for pH 4.8 and 0.50 for pH 7.4, confirming these compositions as the most thermodynamically stable. Compressibility modulus analysis demonstrates that cholesterol enhances monolayer rigidity, with pH 7.4 producing higher values. However, at high cholesterol molar fractions, compressibility modules slightly decrease, suggesting steric constraints and lateral phase separation. The incorporation of magnetite nanoparticles increases molecular area and slightly reduces monolayer rigidity at low cholesterol molar fractions due to steric disruptions, but at cholesterol molar fractions of 0.50 and higher, cholesterol stabilizes the monolayer, counteracting nanoparticle-induced perturbations. These findings provide insight into the thermodynamic and structural regulation of biomimetic lipid monolayers by cholesterol and magnetite nanoparticles, with implications for nanomedicine, membrane biophysics, and lipid-based nanostructures.
Keywords
Cholesterol Dipalmitoylphosphatidylcholine Hydrophobic Magnetite nanoparticles Monolayer stability Surface pressure Phase behavior
Ethical Statement
Ethics committee approval was not required for this study because of there was no study on animals or humans.
References
- Bodik M, Jergel M, Majkova E, Siffalovic P. 2020. Langmuir films of low-dimensional nanomaterials. Adv Colloid Interface Sci, 283: 102239.
- Cullis PR, Hope MJ, Bally MB, Madden TD, Mayer LD, Fenske DB. 1997. Influence of pH gradients on the transbilayer transport of drugs, lipids, peptides, and metal ions into large unilamellar vesicles. Biochim Biophys Acta, 1331: 187-211.
- Dana RM. 1999. The monolayer technique: a potent tool for studying the interfacial properties of antimicrobial and membrane-lytic peptides and their interactions with lipid membranes. Biochim Biophys Acta, 1462: 109-140.
- Ding C, Tong L, Feng J, Fu J. 2016. Recent advances in stimuli-responsive release function drug delivery systems for tumor treatment. Molecules, 21: 1715.
- Ganta S, Devalapally H, Shahiwala A, Amiji M. 2008. A review of stimuli-responsive nanocarriers for drug and gene delivery. J Control Release, 126(3): 187-204.
- Gao W, Chan JM, Farokhzad OC. 2010. pH-responsive nanoparticles for drug delivery. Mol Pharm, 7(6): 1913-20.
- Gong K, Feng SS, Go ML, Soew PH. 2002. Effects of pH on the stability and compressibility of DPPC/cholesterol monolayers at the air-water interface. Colloids Surf. A: Physicochem. Eng Asp, 207: 113-125.
- Hao C, Li J, Mu W, Zhu L, Yang J, Liu T, Li B, Chen S, Sun R. 2016. Adsorption behavior of magnetite nanoparticles into the DPPC model membranes. Appl Surf Sci, 362: 121-125.
- He H, Sun R, Hao C, Yang J, Wang M, Zhang L. 2014. Thermodynamic analysis and AFM study of the interaction of palmitic acid with DPPE in Langmuir monolayers. Colloids Surf. A: Physicochem Eng Asp, 441: 184-194.
- Jurak M. 2013. Thermodynamic aspects of cholesterol effect on properties of phospholipid monolayers: Langmuir and Langmuir−Blodgett monolayer study. J Phys Chem B, 117(12): 3496-3502.
- Jurak M, Mroczka R, Łopucki R. 2018. Properties of artificial phospholipid membranes containing lauryl gallate or cholesterol. J Membr Biol, 251: 277-294.
- Marsh D. 1996. Lateral pressure in membranes. Biochim. Biophys Acta, 1286: 183-223.
- Moya Betancourt SN, Cámara CI, Riva JS. 2023. Interaction between pharmaceutical drugs and polymer-coated Fe3O4 magnetic nanoparticles with Langmuir monolayers as cellular membrane models. Pharmaceutics, 15: 311.
- Oliveira ON Jr, Caseli L, Ariga K. 2022. The past and the future of Langmuir and Langmuir-Blodgett films. Chem Rev, 122: 6459-6513.
- Peetla C, Jin S, Weimer J, Elegbede A, Labhasetwar V. 2014. Biomechanics and thermodynamics of nanoparticle interactions with plasma and endosomal membrane lipids in cellular uptake and endosomal escape. Langmuir, 30: 7522-7532.
- Piosik E, Ziegler-Borowska M, Chełminiak-Dudkiewicz D, Martyński T. 2021. Effect of aminated chitosan-coated Fe3O4 nanoparticles with applicational potential in nanomedicine on DPPG, DSPC, and POPC Langmuir monolayers as cell membrane models. Int J Mol Sci, 22: 2467.
- Rosilio V. 2017. How can artificial lipid models mimic the complexity of molecule-membrane interactions? Adv. Biomembr. Lipid Self-Assembly, 27: 107-141.
- Salas SD, Villanueva ME, Selzer SM, Ferreyra NF, Vico RV. 2024. A systematic study of the impact of aromatic/aliphatic amines and protein corona as coatings of iron oxide magnetic nanoparticles on the interaction with DPPC Langmuir monolayers. Surf Interfaces, 51: 104771.
- Swierczewski M, Bürgi T. 2023. Langmuir and Langmuir−Blodgett films of gold and silver nanoparticles. Langmuir, 39: 2135−2151.
- Szcześ A, Jurak M, Chibowski E. 2012. Stability of binary model membranes—Prediction of the liposome stability by the Langmuir monolayer study. J Colloid Interface Sci, 372: 212-216.
- Torrano AA, Pereira ÂS, Oliveira Jr ON, Barros-Timmons A. 2013. Probing the interaction of oppositely charged gold nanoparticles with DPPG and DPPC Langmuir monolayers as cell membrane models. Colloids Surf B: Biointerfaces, 108: 120-126.
- Vázquez-González ML, Botet-Carreras A, Domènech Ò, Montero TM, Borrell JH. 2019. Planar lipid bilayers formed from thermodynamically-optimized liposomes as new featured carriers for drug delivery systems through human skin. Int J Pharm, 563: 1-8.
- Wrobel EC, Guimarães IDL, Wohnrath K, Oliveira ON Jr. 2024. Effects induced by η⁶-ᴘ-cymene ruthenium(II) complexes on Langmuir monolayers mimicking cancer and healthy cell membranes do not correlate with their toxicity. Biochim Biophys Acta Biomembr, 1866: 184332.
- Zhang W, Wang F, Wang Y, Wang J, Yu Y, Guo S, Chen R, Zhou D. 2016. pH and near-infrared light dual-stimuli responsive drug delivery using DNA-conjugated gold nanorods for effective treatment of multidrug resistant cancer cells. J Control Release, 82: 204.
Details
| Primary Language | English |
|---|---|
| Subjects | Chemical Engineering (Other) |
| Journal Section | Research Articles |
| Authors | |
| Publication Date | May 15, 2025 |
| Submission Date | March 5, 2025 |
| Acceptance Date | April 9, 2025 |
| Published in Issue | Year 2025 Volume: 8 Issue: 3 |
