Nano Research

, Volume 7, Issue 8, pp 1195–1204 | Cite as

Surface properties of encapsulating hydrophobic nanoparticles regulate the main phase transition temperature of lipid bilayers: A simulation study

  • Xubo Lin
  • Ning GuEmail author
Research Article


The main phase transition temperature of a lipid membrane, which is vital for its biomedical applications such as controllable drug release, can be regulated by encapsulating hydrophobic nanoparticles into the membrane. However, the exact relationship between surface properties of the encapsulating nanoparticles and the main phase transition temperature of a lipid membrane is far from clear. In the present work, we performed coarse-grained molecular dynamics simulations to meet this end. The results show the surface roughness of nanoparticles and the density of surface-modifying molecules on the nanoparticles are responsible for the regulation. Increasing the surface roughness of the nanoparticles increases the main phase transition temperature of the lipid membrane, whereas it can be decreased in a nonlinear way via increasing the density of surface-modifying molecules on the nanoparticles. The results may provide insights for understanding recent experimental studies and promote the applications of nanoparticles in controllable drug release by regulating the main phase transition temperature of lipid vesicles.


lipid bilayer phase transition nanoparticle surface roughness density surface molecules 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

12274_2014_482_MOESM1_ESM.pdf (2 mb)
Supplementary material, approximately 1.95 MB.


  1. [1]
    Al-Jamal, W.; Kostarelos, K. Liposome-nanoparticle hybrids for multimodal diagnostic and therapeutic applications. Nanomedicine 2007, 2, 85–98.CrossRefGoogle Scholar
  2. [2]
    Zhang, L. F.; Granick, S. How to stabilize phospholipid liposomes (using nanoparticles). Nano Lett. 2006, 6, 694–698.CrossRefGoogle Scholar
  3. [3]
    Wang, B.; Zhang, L. F.; Bae, S. C.; Granick, S. Nanoparticle-induced surface reconstruction of phospholipid membranes. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 18171–18175.CrossRefGoogle Scholar
  4. [4]
    Urban, A. S.; Fedoruk, M.; Horton, M. R.; Rädler, J. O.; Stefani, F. D.; Feldmann, J. Controlled nanometric phase transitions of phospholipid membranes by plasmonic heating of single gold nanoparticles. Nano Lett. 2009, 9, 2903–2908.CrossRefGoogle Scholar
  5. [5]
    Chen, Y. J.; Bose, A.; Bothun, G. D. Controlled release from bilayer-decorated magnetoliposomes via electromagnetic heating. ACS Nano 2010, 4, 3215–3221.CrossRefGoogle Scholar
  6. [6]
    Amstad, E.; Kohlbrecher, J.; Müller, E.; Schweizer, T.; Textor, M.; Reimhult, E. Triggered release from liposomes through magnetic actuation of iron oxide nanoparticle containing membranes. Nano Lett. 2011, 11, 1664–1670.CrossRefGoogle Scholar
  7. [7]
    An, X. Q.; Zhan, F.; Zhu, Y. Y. Smart photothermal-triggered bilayer phase transition in AuNPs-liposomes to release drug. Langmuir 2013, 29, 1061–1068.CrossRefGoogle Scholar
  8. [8]
    Gopalakrishnan, G.; Danelon, C.; Izewska, P.; Prummer, M.; Bolinger, P.-Y.; Geissbhler, I.; Demurtas, D.; Dubochet, J.; Vogel, H. Multifunctional lipid/quantum dot hybrid nanocontainers for controlled targeting of live cells. Angew. Chem. Int. Ed. 2006, 45, 5478–5483.CrossRefGoogle Scholar
  9. [9]
    Marshall, J. D.; Schnitzer, M. J. Optical strategies for sensing neuronal voltage using quantum dots and other semiconductor nanocrystals. ACS Nano 2013, 7, 4601–4609.CrossRefGoogle Scholar
  10. [10]
    Qiao, R.; Roberts, A. P.; Mount, A. S.; Klaine, S. J.; Ke, P. C. Translocation of C60 and its derivatives across a lipid bilayer. Nano Lett. 2007, 7, 614–619.CrossRefGoogle Scholar
  11. [11]
    Lin, X. B.; Li, Y.; Gu, N. Nanoparticle’s size effect on its translocation across a lipid bilayer: A molecular dynamics simulation. J. Comput. Theor. Nanosci. 2010, 7, 269–276.CrossRefGoogle Scholar
  12. [12]
    Ginzburg, V. V.; Balijepalli, S. Modeling the thermodynamics of the interaction of nanoparticles with cell membranes. Nano Lett. 2007, 7, 3716–3722.CrossRefGoogle Scholar
  13. [13]
    Nangia, S.; Sureshkumar, R. Effects of nanoparticle charge and shape anisotropy on translocation through cell membranes. Langmuir 2012, 28, 17666–17671.CrossRefGoogle Scholar
  14. [14]
    Wang, H. M.; Michielssens, S.; Moors, S. L. C.; Ceulemans, A. Molecular dynamics study of dipalmitoylphosphatidylcholine lipid layer self-assembly onto a single-walled carbon nanotube. Nano Res. 2009, 2, 945–954.CrossRefGoogle Scholar
  15. [15]
    Lehn, R. C. V.; Atukorale, P. U.; Carney, R. P.; Yang, Y. S.; Stellacci, F.; Irvine, D. J.; Alexander-Katz, A. Effect of particle diameter and surface composition on the spontaneous fusion of monolayer-protected gold nanoparticles with lipid bilayers. Nano Lett. 2013, 13, 4060–4067.CrossRefGoogle Scholar
  16. [16]
    Grzelczak, M.; Perez-Juste, J.; Mulvaney, P.; Liz-Marzan, L. M. Shape control in gold nanoparticle synthesis. Chem. Soc. Rev. 2008, 37, 1783–1791.CrossRefGoogle Scholar
  17. [17]
    Alkilany, A. M.; Lohse, S. E.; Murphy, C. J. The gold standard: Gold nanoparticle libraries to understand the nanobio interface. Acc. Chem. Res. 2013, 46, 650–661.CrossRefGoogle Scholar
  18. [18]
    Sun, Y. Controlled synthesis of colloidal silver nanoparticles inorganic solutions: Empirical rules for nucleation engineering. Chem. Soc. Rev. 2013, 42, 2497–2511.CrossRefGoogle Scholar
  19. [19]
    Kim, S. T.; Saha, K.; Kim, C.; Rotello, V. M. The role of surface functionality in determining nanoparticle cytotoxicity. Acc. Chem. Res. 2013, 46, 681–691.CrossRefGoogle Scholar
  20. [20]
    Rasch, M. R.; Rossinyol, E.; Hueso, J. L.; Goodfellow, B. W.; Arbiol, J.; Korgel, B. A. Hydrophobic gold nanoparticle self-assembly with phosphatidylcholine lipid: Membraneloaded and Janus vesicles. Nano Lett. 2010, 10, 3733–3739.CrossRefGoogle Scholar
  21. [21]
    Rasch, M. R.; Yu, Y.; Bosoy, C.; Goodfellow, B. W.; Korgel, B. A. Chloroform-enhanced incorporation of hydrophobic gold nanocrystals into dioleoylphosphatidylcholine (DOPC) vesicle membranes. Langmuir 2012, 28, 12971–12981.CrossRefGoogle Scholar
  22. [22]
    Lee, H.-Y.; Shin, S. H. R.; Abezgauz, L. L.; Lewis, S. A.; Chirsan, A. M.; Danino, D. D.; Bishop, K. J. M. Integration of gold nanoparticles into bilayer structures via adaptive surface chemistry. J. Am. Chem. Soc. 2013, 135, 5950–5953.CrossRefGoogle Scholar
  23. [23]
    Park, S.-H.; Oh, S.-G.; Mun, J.-Y.; Han, S.-S. Effects of silver nanoparticles on the fluidity of bilayer in phospholipid liposome. Colloid Surf. B 2005, 44, 117–122.CrossRefGoogle Scholar
  24. [24]
    Park, S.-H.; Oh, S.-G.; Mun, J.-Y.; Han, S.-S. Loading of gold nanoparticles inside the DPPC bilayers of liposome and their effects on membrane fluidities. Colloid Surf. B 2006, 48, 112–118.CrossRefGoogle Scholar
  25. [25]
    Bothun, G. D. Hydrophobic silver nanoparticles trapped in lipid bilayers: Size distribution, bilayer phase behavior, and optical properties. J. Nanobiotechnol. 2008, 6, 13.CrossRefGoogle Scholar
  26. [26]
    White, G. V.; Chen, Y. J.; Roder-Hanna, J.; Bothun, G. D.; Kitchens, C. L. Structural and thermal analysis of lipid vesicles encapsulating hydrophobic gold nanoparticles. ACS Nano 2012, 6, 4678–4685.CrossRefGoogle Scholar
  27. [27]
    Nagle, J. F. Theory of the main lipid bilayer phase transition. Ann. Rev. Phys. Chem. 1980, 31, 157–195.CrossRefGoogle Scholar
  28. [28]
    Marrink, S. J.; Risselada, H. J.; Yefimov, S.; Tieleman, D. P.; de Vries, A. H. The MARTINI force field: Coarse grained model for biomolecular simulations. J. Phys. Chem. B 2007, 111, 7812–7824.CrossRefGoogle Scholar
  29. [29]
    Ramalho, J. P. P.; Gkeka, P.; Sarkisov, L. Structure and phase transformations of DPPC lipid bilayers in the presence of nanoparticles: Insights from coarse-grained molecular dynamics simulations. Langmuir 2011, 27, 3723–3730.CrossRefGoogle Scholar
  30. [30]
    Rodgers, J. M.; Sørensen, J.; de Meyer, F. J.-M.; Schiøtt, B.; Smit, B. Understanding the phase behavior of coarse-grained model lipid bilayers through computational calorimetry. J. Phys. Chem. B 2012, 116, 1551–1569.CrossRefGoogle Scholar
  31. [31]
    Hakobyan, D.; Heuer, A. Phase separation in a lipid/cholesterol system: Comparison of coarse-grained and united-atom simulations. J. Phys. Chem. B 2013, 117, 3841–3851.CrossRefGoogle Scholar
  32. [32]
    Waheed, Q.; Tjörnhammar, R.; Edholm, O. Phase transitions in coarse-grained lipid bilayers containing cholesterol by molecular dynamics simulations. Biophys. J. 2012, 103, 2125–2133.CrossRefGoogle Scholar
  33. [33]
    Marrink, S. J.; Tieleman, D. P. Perspective on the Martini model. Chem. Soc. Rev. 2013, 42, 6801–6822.CrossRefGoogle Scholar
  34. [34]
    Li, Y.; Chen, X.; Gu, N. Computational investigation of interaction between nanoparticles and membranes: Hydrophobic/hydrophilic effect. J. Phys. Chem. B 2008, 112, 16647–16653.CrossRefGoogle Scholar
  35. [35]
    Li, Y.; Gu, N. Thermodynamics of charged nanoparticle adsorption on charge-neutral membranes: A simulation study. J. Phys. Chem. B 2010, 114, 2749–2754.CrossRefGoogle Scholar
  36. [36]
    Lin, X. B.; Wang, C. L.; Wang, M.; Fang, K.; Gu, N. Computer simulation of the effects of nanoparticles’ adsorption on the properties of supported lipid bilayer. J. Phys. Chem. C 2012, 116, 17960–17968.CrossRefGoogle Scholar
  37. [37]
    Vácha, R.; Martinez-Veracoechea, F. J.; Frenkel, D. Receptor-mediated endocytosis of nanoparticles of various shapes. Nano Lett. 2011, 11, 5391–5395.CrossRefGoogle Scholar
  38. [38]
    Vácha, R.; Martinez-Veracoechea, F. J.; Frenkel, D. Intracellular release of endocytosed nanoparticles upon a change of ligand-receptor interaction. ACS Nano 2012, 6, 10598–10605.Google Scholar
  39. [39]
    Yue, T. T.; Zhang, X. R. Cooperative effect in receptor-mediated endocytosis of multiple nanoparticles. ACS Nano 2012, 6, 3196–3205.CrossRefGoogle Scholar
  40. [40]
    Li, Y.; Yue, T. T.; Yang, K.; Zhang, X. R. Molecular modeling of the relationship between nanoparticle shape anisotropy and endocytosis kinetics. Biomaterials 2012, 33, 4965–4973.CrossRefGoogle Scholar
  41. [41]
    Huang, C. J.; Zhang, Y.; Yuan, H. Y.; Gao, H. J.; Zhang, S. L. Role of nanoparticle geometry in endocytosis: Laying down to stand up. Nano Lett. 2013, 13, 4546–4550.CrossRefGoogle Scholar
  42. [42]
    Yang, K.; Ma, Y.-Q. Computer simulation of the translocation of nanoparticles with different shapes across a lipid bilayer. Nat. Nanotechnol. 2010, 5, 579–583.CrossRefGoogle Scholar
  43. [43]
    Ding, H.-M.; Tian, W.-D.; Ma, Y.-Q. Designing nanoparticle translocation through membranes by computer simulations. ACS Nano 2012, 6, 1230–1238.CrossRefGoogle Scholar
  44. [44]
    Ding, H.-M.; Ma, Y.-Q. Controlling cellular uptake of nanoparticles with pH-sensitive polymers. Sci. Rep. 2013, 3, 2804.Google Scholar
  45. [45]
    Berendsen, H. J. C.; Postma, J. P. M.; van Gunsteren, W. F.; DiNola, A.; Haak, J. R. Molecular dynamics with coupling to an external bath. J. Chem. Phys. 1984, 81, 3684–3690.CrossRefGoogle Scholar
  46. [46]
    Humphrey, W.; Dalke, A.; Schulten, K. VMD: Visual molecular dynamics. J. Mol. Graph. 1996, 14, 33–38.CrossRefGoogle Scholar
  47. [47]
    Hess, B.; Kutzner, C.; van der Spoel, D.; Lindahl, E. GROMACS 4: Algorithms for highly efficient, load-balanced, and scalable molecular simulation. J. Chem. Theory Comput. 2008, 4, 435–447.CrossRefGoogle Scholar
  48. [48]
    Koynova, R.; Caffrey, M. Phases and phase transitions of the phosphatidylcholines. Biochim. Biophys. Acta 1998, 1376, 91–145.CrossRefGoogle Scholar
  49. [49]
    Nagle, J. F.; Tristram-Nagle, S. Structure of lipid bilayers. Biochim. Biophys. Acta 2000, 1469, 159–195.CrossRefGoogle Scholar
  50. [50]
    Kong, X.; Qin, S. S.; Lu, D. N.; Liu, Z. Surface tension effects on the phase transition of a DPPC bilayer with and without protein: A molecular dynamics simulation. Phys. Chem. Chem. Phys. 2014, 16, 8434–8440.CrossRefGoogle Scholar
  51. [51]
    Marrink, S. J.; Risselada, J.; Mark, A. E. Simulation of gel phase formation and melting in lipid bilayers using a coarse grained model. Chem. Phys. Lipids 2005, 135, 223–244.CrossRefGoogle Scholar
  52. [52]
    Marrink, S. J.; de Vries, A. H.; Mark, A. E. Coarse grained model for semiquantitative lipid simulations. J. Phys. Chem. B 2004, 108, 750–760.CrossRefGoogle Scholar
  53. [53]
    Mecke, A.; Majoros, I. J.; Patri, A. K.; Baker Jr, J. R.; Holl, M. M. B.; Orr, B. G. Lipid bilayer disruption by polycationic polymers: The roles of size and chemical functional group. Langmuir 2005, 21, 10348–10354.CrossRefGoogle Scholar
  54. [54]
    Shen, C. Y.; Lazouskaya, V.; Zhang, H. Y.; Wang, F.; Li, B. G.; Jin, Y.; Huang, Y. F. Theoretical and experimental investigation of detachment of colloids from rough collector surfaces. Colloid Surf. A 2012, 410, 98–110.CrossRefGoogle Scholar
  55. [55]
    Shen, C. Y.; Wang, F.; Li, B. G.; Jin, Y.; Wang, L.-P.; Huang, Y. F. Application of DLVO energy map to evaluate interactions between spherical colloids and rough surfaces. Langmuir 2012, 28, 14681–14692.CrossRefGoogle Scholar
  56. [56]
    Shen, C. Y.; Lazouskaya, V.; Zhang, H. Y.; Li, B. G.; Jin, Y.; Huang, Y. F. Influence of surface chemical heterogeneity on attachment and detachment of microparticles. Colloid Surf. A 2013, 433, 14–29.CrossRefGoogle Scholar

Copyright information

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.State Key Laboratory of Bioelectronics and Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science & Medical EngineeringSoutheast UniversityNanjingChina

Personalised recommendations