Skip to main content
SpringerLink
Log in

Geometrical Characterization of an Electropore from Water Positional Fluctuations

  • Published:
The Journal of Membrane Biology Aims and scope Submit manuscript

Abstract

We present here a new method for calculating the radius of a transmembrane pore in a phospholipid bilayer. To compare size-related properties of pores in bilayers of various compositions, generated and maintained under different physical and chemical conditions, reference metrics are needed. Operational metrics can be associated with some observed behavior. For example, pore size can be defined by the largest object that will pass through the length of the pore. The novelty of the present approach resides in the characterization of electropore geometry via a statistical approach, based on essential dynamics rules. We define the pore size geometrically with an algorithm for determining the pore radius. In particular, we extract the radius from the tri-dimensional surface of a defined pore region. The method is applied to a pore formed in a phospholipid bilayer by application of an external electric field. Although the details described here are specific for lipid pores in molecular dynamics simulations, the method can be generalized for any kind of pores for which appropriate structural information is available.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Amadei A, Marracino P (2015) Theoretical–computational modelling of the electric field effects on protein unfolding thermodynamics. RSC Adv 5:96551–96561

    Article  CAS  Google Scholar 

  • Amadei A, Linssen ABM, Berendsen HJC (1993) Essential dynamics of proteins. Proteins 17:412–425

    Article  CAS  PubMed  Google Scholar 

  • Avena M, Marracino P, Liberti M, Apollonio F, English NJ (2015) Communication: influence of nanosecond-pulsed electric fields on water and its subsequent relaxation: dipolar effects and debunking memory. J Chem Phys 142(14):141101

    Article  PubMed  Google Scholar 

  • Berendsen HJC, Postma JPM, van Gunsteren WF, Hermans J (1981) Interaction models for water in relation to protein hydration. In: Pullman B (ed) Intermolecular Forces. Springer, Dordrecht, pp 331–342

    Chapter  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

    Article  CAS  Google Scholar 

  • Berger O, Edholm O, Jahnig F (1997) Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature. Biophys J 72(5):2002–2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Böckmann RA, de Groot BL, Kakorin S, Neumann E, Grubmüller H (2008) Kinetics, statistics, and energetics of lipid membrane electroporation studied by molecular dynamics simulations. Biophys J 95(4):1837–1850

    Article  PubMed  PubMed Central  Google Scholar 

  • Bussi G, Donadio D, Parrinello M (2007) Canonical sampling through velocity-rescaling. J Chem Phys 126(1):014101

    Article  PubMed  Google Scholar 

  • Casciola M, Bonhenry D, Liberti M, Apollonio F, Tarek M (2014) A molecular dynamic study of cholesterol rich lipid membranes: comparison of electroporation protocols. Bioelectrochemistry 100:11–17

    Article  CAS  PubMed  Google Scholar 

  • Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LGJA (1995) A smooth particle mesh Ewald method. Chem Phys 103(19):8577–8593

    CAS  Google Scholar 

  • Fernandez ML, Risk M, Reigada R, Vernier PT (2012) Size-controlled nanopores in lipid membranes with stabilizing electric fields. Biochem Bioph Res Commun 423:325–330

    Article  CAS  Google Scholar 

  • Gurtovenko AA, Vattulainen I (2005) Pore formation coupled to ion transport through lipid membranes as induced by transmembrane ionic charge imbalance: atomistic molecular dynamics study. J Am Chem Soc 127:17570–17571

    Article  CAS  PubMed  Google Scholar 

  • Gurtovenko AA, Vattulainen I (2007) Ion leakage through transient water pores in protein-free lipid membranes driven by transmembrane ionic charge imbalance. Biophys J 92:1878–1890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hess B, Bekker H, Berendsen HJC, Fraaije JGEMJ (1997) 3 LINCS: a linear constraint solver for molecular simulations. Comput Chem 18(12):1463–1472

    Article  CAS  Google Scholar 

  • Ho MC, Casciola M, Levine ZA, Vernier PT (2013) Molecular dynamics simulations of ion conductance in field-stabilized nanoscale lipid electropores. J Phys Chem B 117:11633–11640

    Article  CAS  PubMed  Google Scholar 

  • Humphrey W, Dalke A, Schulten K (1996) VMD — Visual molecular dynamics. J Mol Graphics 14:33–38. http://www.ks.uiuc.edu/Research/vmd/allversions/cite.html

  • Leontiadou H, Mark AE, Marrink SJ (2004) Molecular dynamics simulations of hydrophilic pores in lipid bilayers. Biophys J 86:2156–2164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leontiadou H, Alan EM, Marrink SJ (2007) Ion transport across transmembrane pores. Biophys J 92:4209–4215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levine ZA, Vernier PT (2010) Life cycle of an electropore: field-dependent and field-independent steps in pore creation and annihilation. J Membr Biol 236:27–36

    Article  CAS  PubMed  Google Scholar 

  • Marracino P, Amadei A, Apollonio F, d’Inzeo G, Liberti M, di Crescenzo A, Fontana A, Zappacosta R, Aschi M (2011) Modeling of chemical reactions in micelle: water-mediated Keto-Enol interconversion as a case study. J Phys Chem B 115(25):8102–8111

    Article  CAS  PubMed  Google Scholar 

  • Marracino P, Apollonio F, Liberti M, d’Inzeo G, Amadei A (2013) Effect of high exogenous electric pulses on protein conformation: myoglobin as a case study. J Phys Chem B 117(8):2273–2279

    Article  CAS  PubMed  Google Scholar 

  • Marracino P, Casciola M, Liberti M, Apollonio F (2014) Evaluation of protein electrostatic potential from molecular dynamics simulations in the presence of exogenous electric fields: the case study of myoglobin. In:W. Rocchia, M. Spagnuolo computational electrostatics for biological applications, Springer, New York (2015), pp 255–270

  • Marracino P, Liberti M, d’Inzeo G, Apollonio F (2015) Water response to intense electric fields: a molecular dynamics study. Bioelectromagnetics 36:377

    Article  CAS  PubMed  Google Scholar 

  • Marty M, Sersa G, Garbay JR, Gehl J, Collins CG, Snoj M, Billard V, Geertsen PF, Larkin JO, Miklavcic D (2006) Electrochemotherapy — An easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study. EJC Suppl 4:3–13

    Article  CAS  Google Scholar 

  • Miyamoto S, Kollman PA (1992) SETTLE: an analytical version of the SHAKE and RATTLE Algorithm for Rigid Water Models. J Comput Chem 13(8):952–962

    Article  CAS  Google Scholar 

  • Neumann E, Kakorin S, Toensing K (1999) Fundamentals of electroporative delivery of drugs and genes. Bioelectrochem Bioenerg 48:3–16

    Article  CAS  PubMed  Google Scholar 

  • Pellegrini-Calace M, Maiwald T, Thornton JM (2009) Pore Walker: a novel tool for the identification and characterization of channels in transmembrane proteins from their three-dimensional structure. PLoS Comput Biol 5:e1000440

    Article  PubMed  PubMed Central  Google Scholar 

  • Petrek M, Kosinova P, Koca J, Otyepka M (2007) MOLE: a Voronoi diagram-based explorer of molecular channels, pores, and tunnels. Structure 15:1357–1363. doi:10.1016/j.str.2007.10.007

    Article  CAS  PubMed  Google Scholar 

  • Reale R, English NJ, Garate JA, Marracino P, Liberti M, Apollonio F (2013) Human aquaporin 4 gating dynamics under and after nanosecond-scale static and alternating electric-field impulses: a molecular dynamics study of field effects and relaxation. J Chem Phys 139(20):205101

    Article  PubMed  Google Scholar 

  • Reale R, English NJ, Marracino P, Liberti M, Apollonio F (2014) Dipolar response and hydrogen-bond kinetics in liquid water in square-wave time-varying electric fields. Mol Phys 112(14):1870–1878

    Article  CAS  Google Scholar 

  • Smart OS, Neduvelil JG, Wang X, Wallace BA, Sansom MS (1996) HOLE: a program for the analysis of the pore dimensions of ion channel structural models. J Mol Gr 14:354–360

    Article  CAS  Google Scholar 

  • Tarek M (2005) Membrane electroporation: a molecular dynamics simulation. Biophys J 88:4045–4053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tessie J, Golzio M, Rols MP (2005) Mechanisms of cell membrane electropermeabilization: a mini review of our present (lack of?) knowledge. Biochim Biophys Acta 1724:270–280

    Article  Google Scholar 

  • Tieleman DP (2004) The molecular basis of electroporation. BMC Biochem 5:10

    Article  PubMed  PubMed Central  Google Scholar 

  • Uematsu M, Frank EU (1980) Static dielectric constant of water and steam. J Phys Chem Ref Data 9(4):1291–1306

    Article  CAS  Google Scholar 

  • Van der Spoel D, Lindahl E, Hess B, and the GROMACS Development Team (2014) GROMACS User Manual version 4.6.6. www.gromacs.org

  • Vernier PT, Ziegler MJ, Dimova R (2009) Calcium binding and head group dipole angle in phosphatidylserine: phosphatidylcholine bilayers. Langmuir 25(2):1020–1027

    Article  CAS  PubMed  Google Scholar 

  • Ziegler MJ, Vernier PT (2008) Interface water dynamics and porating electric fields for phospholipid bilayers. J Phys Chem B 112:13588–13596

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Funding

This project received support within the framework of the Joint IIT-Sapienza LAB on Life-NanoScience Project (81/13 16-04-2013) and from the Sapienza University of Rome, Research Projects, 2015 (C26A15T3T2). Castellani F and Vernier PT were supported by Air Force Office of Scientific Research Grant FA9550-14-1-0123, AFOSR MURI Grant FA9550-15-1-0517, Old Dominion University Biomedical Engineering Institute, and the Frank Reidy Research Center for Bioelectrics. Computational resources were provided by Old Dominion University High Performance Computing (http://www.odu.edu/hpc/) and the University of Southern California Center for High Performance Computing (http://hpcc.usc.edu/).

Author information

Authors and Affiliations

  1. Department of Information Engineering, Electronics, and Telecommunications, Sapienza University of Rome, Rome, Italy

    P. Marracino, M. Liberti & F. Apollonio

  2. Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA, 23508, USA

    F. Castellani & P. T. Vernier

  3. Biomedical Engineering Institute, Frank Batten College of Engineering and Technology, Old Dominion University, Norfolk, VA, 23529, USA

    F. Castellani

Authors
  1. P. Marracino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Castellani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. T. Vernier
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Liberti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. F. Apollonio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. Marracino.

Ethics declarations

Conflict of interest

No conflicts of interest, financial or otherwise are declared by the authors.

Animal and human rights statement

This article does not contain any studies with human participants or animals.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 13 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Marracino, P., Castellani, F., Vernier, P.T. et al. Geometrical Characterization of an Electropore from Water Positional Fluctuations. J Membrane Biol 250, 11–19 (2017). https://doi.org/10.1007/s00232-016-9917-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00232-016-9917-y

Keywords

Search

Navigation