Skip to main content

Chemotherapy efficiency increase via shock wave interaction with biological membranes: a molecular dynamics study

Microfluidics and Nanofluidics volume 16, pages 613–622 (2014)Cite this article

Abstract

Application of ultrasound to biological tissues has been identified as a promising cancer treatment technique relying on temporal enhancement of biological membrane permeability via shock wave impact. In the present study, the effects of ultrasonic waves on a 1,2-dipalmitoyl-sn-phosphatidylcholine biological membrane are examined through molecular dynamics simulations. Molecular dynamics methods traditionally employ periodic boundary conditions which, however, restrict the total simulation time to the time required for the shock wave crossing the domain, thus limiting the evaluation of the effects of shock waves on the diffusion properties of the membrane. A novel method that allows capturing both the initial shock wave transit as well as the subsequent longer-timescale diffusion phenomena has been successfully developed, validated and verified via convergence studies. Numerical simulations have been carried out with ultrasonic impulses varying from 0.0 to 0.6 mPa s leading to the conclusion that for impulses ≥0.45 mPa s, no self-recovery of the bilayer is observed and, hence, ultrasound could be applied to the destruction of localized tumor cells. However, for impulses ≤0.3 mPa s, an increase in the transversal diffusivity of the lipids, indicating a consequent enhancement of drug absorption across the membrane, is initially observed followed by a progressive recovery of the initial values, thereby suggesting the advantageous effects of ultrasound on enhancing the chemotherapy efficiency.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price includes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14

References

  • Andoh Y, Ito T, Okazaki S (2012) An application of improved force field to fully hydrated DPPC and POPC bilayers in a tensionless NPT ensemble: a test of CHARMM 27-based new force field by Högberg et al. Mol Simul 38(5):414418. doi:10.1080/08927022.2010.548385

    Article  Google Scholar 

  • Berendsen HJC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR (1984) Molecular dynamics with coupling to an external bath. J Chem Phys 81(8):3684–3690. doi:10.1063/1.448118

    Article  Google Scholar 

  • Bockmann RA, Hac A, Heimburg T, Grubmuller H (2003) Effect of sodium chloride on a lipid bilayer. Biophys J 85(3):1647–1655. doi:10.1016/S0006-3495(03)74594-9

    Article  Google Scholar 

  • Brú A, Casero D (2006) The effect of pressure on the growth of tumour cell colonies. J Theor Biol 243:171–180. doi:10.1016/j.jtbi.2006.05.020

    Article  Google Scholar 

  • Bussi G, Donadio D, Parrinello M (2007) Canonical sampling through velocity rescaling. J Chem Phys 126(1):014–101. doi:10.1063/1.2408420

    Article  Google Scholar 

  • Douliez JP, Leonard A, Dufourc EJ (1995) Restatement of order parameters in biomembranes—calculation of C–C bond order parameters from C–D quadrupolar splittings. Biophys J 68(5):1727–1739

    Article  Google Scholar 

  • Ewald PP (1921) Die Berechnung optischer und eletrostatischer Gitterpotentiale. Ann Phys 369(3):253–287

    Article  Google Scholar 

  • Freites JA, OConnor JW, Tobias DJ, Mondragon-Ramirez C, Vorobyov I, MacKerell AD, Klauda JB, Venable RM and Pastor JW (2010) Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types. J Chem Phys B 114:7830–7843

    Article  Google Scholar 

  • Frigo M, Johnson SG (2005) The design and implementation of FFTW3. Proc IEEE 93(2):216–231. doi:10.1109/JPROC.2004.840301

    Article  Google Scholar 

  • Ganzenmüller GC, Hiermaier S, Steinhauser MO (2011) Shock-wave induced damage in lipid bilayers: a dissipative particle dynamics simulation study. Soft Matter 7:4307–4317. doi:10.1039/C0SM01296C

    Article  Google Scholar 

  • Hess B, Kutzner C, Spoel D, Lindahl E (2008) GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput 4(3):435–447. doi:10.1021/ct700301q

    Article  Google Scholar 

  • Hoover WG (1985) Canonical dynamics: equilibrium phase-space distributions. Phys Rev A 31(3):1695–1697. doi:10.1103/PhysRevA.31.1695

    Article  Google Scholar 

  • Jo S, Kim T, Im W (2007) Automated builder and database of protein/membrane complexes for molecular dynamics simulations. PLoS ONE 2(9):e880. doi:10.1371/journal.pone.0000880

    Article  Google Scholar 

  • Klauda JB, Eldho NV, Gawrisch K, Brooks BR, Pastor RW (2008) Collective and noncollective models of NMR relaxation in lipid vesicles and multilayers. J Phys Chem J 112(19):5924–5929. doi:10.1021/jp075641w

    Article  Google Scholar 

  • Klauda JB, Venable RM, Freites JA, Connor JW, Tobias DJ, Mondragon-Ramirez C, Vorobyov I, MacKerell AD, Pastor RW (2010) Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types. J Phys Chem B 114(23):78307843. doi:10.1021/jp101759q

    Article  Google Scholar 

  • Kodama T, Hamblin MR, Doukas AG (2000) Cytoplasmic molecular delivery with shock waves: importance of impulse. Biophys J 79:1821–1832. doi:10.1016/S0006-3495(00)76432-0

    Article  Google Scholar 

  • Koshiyama K, Kodama T, Yano T, Fijikawa S (2006) Structural change in lipid bilayers and water penetration induced by shock waves: molecular dynamics simulations. Biophys J 91(6):2198–2205. doi:10.1529/biophysj.105.077677

    Article  Google Scholar 

  • Kucerka N, Tristram-Nagle S, Nagle JF (2006) Closer look at structure of fully hydrated fully hydrated fluid phase DPPC bilayers. Biophys J 90(11):L83L85. doi:10.1529/biophysj.106.086017

    Article  Google Scholar 

  • Kucerka N, Nagle JF, Sachs JN, Feller SE, Pencer J, Jackson A, Katsaras J (2008) Lipid bilayer structure determined by the simultaneous analysis of neutron and X-ray scattering data. Biophys J 95(5):2356–2367. doi:10.1529/biophysj.108.132662

    Article  Google Scholar 

  • Nosé S (1984) A molecular dynamics method for simulations in the canonical ensemble. Mol Phys 31(3):1695–1697. doi:10.1080/00268978400101201

    Google Scholar 

  • Parrinello M, Rahman A (1981) Polymorphic transitions in single crystals: a new molecular dynamics method. J Appl Phys 52(12):7182–7190. doi:10.1063/1.328693

    Article  Google Scholar 

  • Seelig A, Seelig J (1974) Dynamic structure of fatty acyl chains in a phospholipid bilayer measured by deuterium magnetic resonance. Biochemistry 13(23):4839–4845. doi:10.1021/bi00720a024

    Article  Google Scholar 

  • Seelig A, Seelig J (1975) Bilayers of dipalmitoyl-3-sn-phosphatidylcholine. Conformational differences between the fatty acyl chains. Biochim Biophys Acta 406(1). doi:10.1016/0005-2736(75)90037-1

  • Singer SJ, Nicholson GL (1972) The fluid mosaic model of the structure of cell membranes. Science 175(4023):720–731. doi:10.1126/science.175.4023.720

    Article  Google Scholar 

  • Sonne J, Jensen MO, Hansen FY, Hemmingsen L, Peter GH (2007) Reparametrization of all-atom dipalmitoylphosphatidylcholine lipid parameters enables simulation. Biophys J 92(12):4157–4167. doi:10.1529/biophysj.106.087130

    Article  Google Scholar 

  • Striolo A (2006) The mechanism of water diffusion in narrow carbon nanotubes. Nano Lett 6(4):633639. doi:10.1021/nl052254u

    Article  Google Scholar 

  • Tieleman DP, Berendsen HJC. (1996) Molecular dynamics simulations of a fully hydrated dipalmitoylphosphatidylcholine bilayer with different macroscopic boundary conditions and parameters. J Chem Phys 105(11):4871–4880. doi:10.1063/1.472323

    Article  Google Scholar 

  • Tieleman DP, Marrink SJ, Berendsen HJC (1997) A computer perspective of membranes: molecular dynamics studies of lipid bilayer systems. Biochim Biophys Acta 1331:235–270. doi:10.1016/S0304-4157(97)00008-7

    Article  Google Scholar 

  • Vogel A, Busch S, Parlitz U (1996) Shock wave emission and cavitation bubble generation by picosecond and nanosecond optical breakdown in water. J Acoust Soc Am 100(1):148–165 doi:10.1121/1.415878

    Article  Google Scholar 

  • World Health Organization (2009) World Health Statistics 2009. Number ISBN 97892 4 156381. World Health Organization

  • Zhao S, Germann TC, Strachan A (2006) Atomistic simulations of shock-induced alloying reactions in Ni/Al nanolaminates. J Chem Phys 125(16):164707–164714. doi:10.1063/1.2359438

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Plasma Science and Fusion Center, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

    Silvia Espinosa

  2. Department of Engineering Physics, Cranfield University, Cranfield, MK43 0AL, UK

    Silvia Espinosa, Nikolaos Asproulis & Dimitris Drikakis

Authors
  1. Silvia Espinosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nikolaos Asproulis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dimitris Drikakis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Silvia Espinosa.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Espinosa, S., Asproulis, N. & Drikakis, D. Chemotherapy efficiency increase via shock wave interaction with biological membranes: a molecular dynamics study. Microfluid Nanofluid 16, 613–622 (2014). https://doi.org/10.1007/s10404-013-1258-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10404-013-1258-x

Keywords

  • Molecular dynamics
  • Impulse
  • Boundary conditions
  • Shock wave
  • Cancer
  • Biological membrane