Changes in the conductivity of bilayer lipid membranes under the action of pluronics L61 and F68: Similarities and differences

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

The effect of pluronics L61 and F68 with the same length of hydrophobic poly(propylene oxide) blocks and different lengths of hydrophilic poly(ethylene oxide) blocks on the conductivity of planar bilayer lipid membranes made of azolectin was investigated. The integral conductivity of the membranes increases with increasing concentrations of both pluronics. With the same concentration of pluronics in solution, the conductivity for L61 is higher. According to the literature data [24]. At close concentrations of membrane-bound pluronics, membrane conductivities are also close. It was concluded that the appearance of identical hydrophobic parts of pluronics L61 and F68 in the membrane causes the same increase in conductivity in the first approximation. The shape of the conductivity-concentration curves is superlinear for L61 and sublinear for F68. In the presence of both pluronics, conduction spikes with an amplitude from 10 to 300 pSm and higher are observed for approximately 40% of the membranes. We associate the observed surges in conductivity with the appearance of conductive pores or defects in the membrane. The number of pores registered in the membrane was a random variable with a large variance and did not correlate with the concentration of pluronic. The difference between the average pore conductivities for membranes with L61 and F68 was not statistically significant.

Full Text

Restricted Access

About the authors

A. A. Anosov

I. M. Sechenov First Moscow State Medical University (Sechenov University); Kotelnikov Institute of Radioengineering and Electronics of Russian Academy of Sciences

Email: ryleeva_e_d@staff.sechenov.ru
Russian Federation, Moscow, 119991; Moscow, 125009

E. D. Borisova

aI. M. Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
Email: ryleeva_e_d@staff.sechenov.ru
Russian Federation, Moscow, 119991

O. O. Konstantinov

aI. M. Sechenov First Moscow State Medical University (Sechenov University)

Email: ryleeva_e_d@staff.sechenov.ru
Russian Federation, Moscow, 119991

E. Yu. Smirnova

aI. M. Sechenov First Moscow State Medical University (Sechenov University)

Email: ryleeva_e_d@staff.sechenov.ru
Russian Federation, Moscow, 119991

E. A. Korepanova

Pirogov Russian National Research Medical University

Email: ryleeva_e_d@staff.sechenov.ru
Russian Federation, Moscow, 117997

V. A. Kazamanov

MIREA – Russian Technological University

Email: ryleeva_e_d@staff.sechenov.ru
Russian Federation, Moscow, 119991

A. S. Derunets

National Research Centre “Kurchatov Institute”

Email: ryleeva_e_d@staff.sechenov.ru
Russian Federation, Moscow, 123182

References

  1. Fusco, S., Borzacchiello, A., and Netti, P.A., Perspectives on: PEO-PPO-PEO triblock copolymers and their biomedical applications, J. Bioact. Compat. Polym., 2006, vol. 21, p. 149. https://doi.org/10.1177/0883911506063207
  2. Rey-Rico, A. and Cucchiarini, M., PEO-PPO-PEO tri-block copolymers for gene delivery applications in human regenerative medicine – an overview, Intern. J. Mol. Sci., 2018, vol. 19, p. 775. https://doi.org/10.3390/ijms19030775
  3. Zarrintaj, P., Ramsey, J.D., Samadi, A., et al., Poloxamer: A versatile tri-block copolymer for biomedical applications, Acta Biomater., 2020, vol. 110, p. 37. https://doi.org/10.1016/j.actbio.2020.04.028
  4. Frey, S.L. and Lee, K.Y.C., Temperature dependence of poloxamer insertion into and squeeze-out from lipid monolayers, Langmuir, 2007, vol. 23, p. 2631. https://doi.org/10.1021/la0626398
  5. Yu, J., Qiu, H., Yin, S., Wang, H., and Li, Y., Polymeric Drug Delivery System Based on Pluronics for Cancer Treatment, Molecules, 2021, vol. 26, p. 3610. https://doi.org/10.3390/molecules26123610
  6. Prado-Audelo, J.J., Magaña, B.A., et al., In vitro cell uptake evaluation of curcumin-loaded PCL/F68 nanoparticles for potential application in neuronal diseases, J. Drug Delivery Sci. and Technol., 2019, vol. 52, p. 905.
  7. Venne, A., Li, S., Mandeville, R., Kabanov, A., and Alakhov, V., Hypersensitizing effect of pluronic L61 on cytotoxic activity, transport, and subcellular distribution of doxorubicin in multiple drug-resistant cells, Cancer Res., 1996, vol. 56(16), p. 3626.
  8. Huang, J., Si, L., Jiang, L., Fan, Z., Qiu, J., and Li, G., Effect of pluronic F68 block copolymer on P-glycoprotein transport and CYP3A4 metabolism, Intern. J. Pharm., 2008, vol. 356, p. 351.
  9. Chang, L.C., Lin, C.Y., Kuo, M.W., et al., Interactions of Pluronics with phospholipid monolayers at the air–water interface, J. Colloid Interface Sci., 2005, vol. 285, p. 640. https://doi.org/10.1016/j.jcis.2004.11.011
  10. Wu, G., Majewski, J, Ege, C., et al., Interaction between lipid monolayers and poloxamer 188: an X-ray reflectivity and diffraction study, Biophys. J., 2005, vol. 89, p. 3159. https://doi.org/10.1529/biophysj.104.052290
  11. Maskarinec, S.A., Hannig, J., Lee, R.C., et al., Direct observation of poloxamer 188 insertion into lipid monolayers, Biophys. J., 2002, vol. 82, p. 1453. https://doi.org/10.1016/S0006-3495(02)75499-4
  12. Krylova, O.O., Melik-Nubarov, N.S., Badun, G.A., Ksenofontov, A.L., Menger, F.L., and Yaroslavov, A.A., Pluronic L61 accelerates flip-flop and transbilayer doxorubicin permeation, Chemistry, 2003, vol. 9 (16), p. 3930.
  13. Zhirnov, A.E., Demina, T.V., Krylova, O.O., Grozdova, I.D., and Melik-Nubarov, N.S., Lipid composition determines interaction of liposome membranes with Pluronic L61, Biochim. Biophys. Acta, 2005, vol. 1720(1–2), p. 73.
  14. Erukova, V.Y., Krylova, O.O., Antonenko, Y.N., and Melik-Nubarov, N.S., Effect of ethylene oxide and propylene oxide block copolymers on the permeability of bilayer lipid membranes to small solutes including doxorubicin, Biochim. Biophys. Acta, 2000, vol. 1468(1–2), p. 73.
  15. Cheng, C.Y., Wang, J.Y., Kausik, R., et al., Nature of interactions between PEO-PPO-PEO triblock copolymers and lipid membranes:(II) role of hydration dynamics revealed by dynamic nuclear polarization, Biomacromolecules, 2012, vol. 13, p. 2624. https://doi.org/10.1021/bm300848c
  16. Ileri Ercan, N., Stroeve, P., Tringe, J.W., et al., Understanding the interaction of pluronics L61 and L64 with a DOPC lipid bilayer: an atomistic molecular dynamics study, Langmuir, 2016, vol. 32, p. 10026. https://doi.org/10.1021/acs.langmuir.6b02360
  17. Hezaveh, S., Samanta, S., De Nicola, A., et al., Understanding the interaction of block copolymers with DMPC lipid bilayer using coarse-grained molecular dynamics simulations, J. Phys. Chem. B, 2012, vol. 116, p.14333. https://doi.org/10.1021/jp306565e
  18. Rabbel, H., Werner, M., and Sommer, J.U., Interactions of amphiphilic triblock copolymers with lipid membranes: modes of interaction and effect on permeability examined by generic Monte Carlo simulations, Macromolecules, 2015, vol. 48, p. 4724.
  19. Zaki, A.M. and Carbone, P., How the incorporation of Pluronic block copolymers modulates the response of lipid membranes to mechanical stress, Langmuir, 2017, vol. 33, p. 13284. https://doi.org/10.1021/acs.langmuir.7b02244
  20. Krylova, O.O. and Pohl, P., Ionophoric activity of pluronic block copolymers, Biochemistry, 2004, vol. 43, p. 3696. https://doi.org/10.1021/bi035768l
  21. Anosov, A. A., Smirnova, E. Y., Korepanova, E. A., Kazamanov, V. A., and Derunets, A. S., Different effects of two Poloxamers (L61 and F68) on the conductance of bilayer lipid membranes, Europ. Phys. J. E, 2023, vol. 46(3), p. 14. https://doi.org/10.1140/epje/s10189-023-00270-1
  22. Mueller, P., Rudin, D.O., Tien, H. T., and Wescott, W. C., Reconstitution of excitable cell membrane structure in vitro, Circulation, 1962, 26:1167.
  23. Antonov, V.F., Smirnova, E.Y., Anosov, A.A., et al., PEG blocking of single pores arising on phase transitions in unmodified lipid bilayers, Biophysics, 2008, vol. 53 (5), p. 390. https://doi.org/10.1134/S0006350908050126
  24. Grozdova, I.D., Badun, G.A., Chernysheva, M.G., et al., Increase in the length of poly (ethylene oxide) blocks in amphiphilic copolymers facilitates their cellular uptake, J. Appl. Polym. Sci., 2017, vol. 134, p. 45492. https://doi.org/10.1002/app.45492
  25. Tristram-Nagle, S., Kim, D.J., Akhunzada, N., et al., Structure and water permeability of fully hydrated diphytanoylPC, Chem. Phys. Lipids, 2010, vol. 163, p. 630. https://doi.org/10.1016/j.chemphyslip.2010.04.011
  26. Рытов, С. М. Введение в статистическую радиофизику. М.: Наука, 1976. С. 36–41. [Rytov, S.M., Introduction to Statistical Radiophysics (in Russian), Moscow: Science, 1976, p. 36–41.]
  27. Abidor, I.G., Arakelyan, V.B., Chernomordik, L.V., et al., Electric breakdown of bilayer lipid membranes: I. The main experimental facts and their qualitative discussion, J. Electroanal. Chem. Interfacial Electrochem., 1979, vol. 104, p. 37. https://doi.org/10.1016/S0022-0728(79)81006-2
  28. Glaser, R.W., Leikin, S.L., Chernomordik, L.V., et al., Reversible electrical breakdown of lipid bilayers: formation and evolution of pores, Biochim. Biophys. Acta, Biomembr., 1988, vol. 940, p. 275. https://doi.org/10.1016/0005-2736(88)90202-7
  29. Weaver, J.C. and Chizmadzhev, Y.A., Theory of electroporation: a review, Bioelectrochem. Bioenerg., 1996, vol. 41, p. 135. https://doi.org/10.1016/S0302-4598(96)05062-3
  30. Böckmann, R.A., De Groot, B.L., Kakorin, S., et al., Kinetics, statistics, and energetics of lipid membrane electroporation studied by molecular dynamics simulations, Biophys. J., 2008, vol. 95, p. 1837. https://doi.org/10.1529/biophysj.108.129437
  31. Kirsch, S.A. and Böckmann, R.A., Membrane pore formation in atomistic and coarse-grained simulations, Biochim. Biophys. Acta, Biomembr., 2016, vol. 1858, p. 2266. https://doi.org/10.1016/j.bbamem.2015.12.031
  32. Bennett, W.D., Sapay, N., and Tieleman, D.P., Atomistic simulations of pore formation and closure in lipid bilayers, Biophys. J., 2014, vol. 106, p. 210. https://doi.org/10.1016/j.bpj.2013.11.4486
  33. Melikov, K.C., Frolov, V.A., Shcherbakov, A., et al., Voltage-induced nonconductive pre-pores and metastable single pores in unmodified planar lipid bilayer, Biophys. J., 2001, vol. 80, p. 1829. https://doi.org/10.1016/S0006-3495(01)76153-X
  34. Dehez, F., Delemotte, L., Kramar, P., et al., Evidence of conducting hydrophobic nanopores across membranes in response to an electric field, J. Phys. Chem. C, 2014, vol. 118, p. 6752. https://doi.org/10.1021/jp4114865
  35. Anosov, A.A., Smirnova, E.Y., Sharakshane, A.A., et al., Increase in the current variance in bilayer lipid membranes near phase transition as a result of the occurrence of hydrophobic defects, Biochim. Biophys. Acta, Biomembr., 2020, vol. 1862, p. 183147. https://doi.org/10.1016/j.bbamem.2019.183147
  36. Akimov, S.A., Volynsky, P.E., Galimzyanov, T.R., et al., Pore formation in lipid membrane I: Continuous reversible trajectory from intact bilayer through hydrophobic defect to transversal pore, Sci. Rep., 2017, vol. 7, p. 1. https://doi.org/10.1038/s41598-017-12127-7
  37. Hub, J.S. and Awasthi, N., Probing a continuous polar defect: A reaction coordinate for pore formation in lipid membranes, J. Chem. Theory Comput., 2017, vol. 13, p. 2352. https://doi.org/10.1021/acs.jctc.7b00106
  38. Ting, C.L., Awasthi, N., Müller, M., et al., Metastable prepores in tension-free lipid bilayers, Phys. Rev. Lett., 2018, vol. 120, p. 128103. https://doi.org/10.1103/PhysRevLett.120.128103
  39. Bubnis, G. and Grubmüller, H., Sequential water and headgroup merger: Membrane poration paths and energetics from MD simulations, Biophys. J., 2022, vol. 119, p. 2418. https://doi.org/10.1016/j.bpj.2020.10.037

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Additional materials
Download (132KB)
3. Fig. 1. Experimental dependences of the specific conductivity of azolectin membranes (a) on the concentration of L61 and F68 in the surrounding solution, (b) on the relative concentration of Pluronics bound to the membrane; approximating dependences of the specific conductivity g on the concentration C of Pluronics in solution: gL₆₁ = 15.3 × C¹.³ and gF₆₈ = 12.9 × C ⁰.⁷ pS/mm²; conductivity of control membranes 42 ± 6 pS/mm². The applied voltage did not exceed 50 mV. Surrounding solution: 0.1 M KCl. Standard errors are given.

Download (158KB)
4. Fig. 2. Stepped tracks and histograms of conductivity of azolectin membranes in 0.1 M KCl: (a) control, (b) with the addition of 12 μM L61, (c) 26 μM F68. Voltage on the membrane is 25 mV.

Download (351KB)
5. Fig. 3. Conductivity tracks and histograms of azolectin membranes in 0.1 M KCl: (a) with the addition of 8 μM L61, (b) 26 μM F68. The voltage on the membrane is 25 mV.

Download (211KB)
6. Fig. 4. Fluctuations in the conductivity of azolectin membranes in 0.1 M KCl with the addition of 16 μM L61: (a) track, (b) histogram, (c) section of the track on an enlarged scale, (d) autocorrelation function of conductivity calculated from experimental data and approximated by an exponential. Voltage on the membrane is 25 mV.

Download (237KB)
7. Fig. 5. Fluctuations in the conductivity of azolectin membranes in 0.1 M KCl with the addition of 26 μM F68: (a) track, (b) histogram (a local maximum in the region of 60 pS is shown, the histogram maximum is at 28 pS), (c) a section of the track on an enlarged scale, (d) autocorrelation function of conductivity calculated from experimental data and approximated by an exponential. The voltage on the membrane is 25 mV.

Download (255KB)

Copyright (c) 2024 Russian Academy of Sciences