Molecular dynamics study of accelerated ion-induced shock waves in biological media

Eur. Phys. J. D (2016) 70: 183 DOI: 10.1140/epjd/e2016-70281-7 THE EUROPEAN PHYSICAL JOURNAL D Regular Article Molecular dynamics study of accelerated ion-induced shock waves in biological media Pablo de Vera1,2,3,a , Nigel J. Mason2 , Fred J. Currell1 , and Andrey V. Solov’yov3,b 1 School of Mathematics and Physics, Queen’s University Belfast, BT7 1NN Belfast, Northern Ireland, UK Department of Physical Sciences, The Open University, Walton Hall, MK7 6AA Milton Keynes, England, UK 3 MBN Research Center, Altenhöferallee 3, 60438 Frankfurt am Main, Germany 2 Received 20 April 2016 / Received in final form 28 June 2016 Published online 6 September 2016 c The Author(s) 2016. This article is published with open access at Springerlink.com  Abstract. We present a molecular dynamics study of the effects of carbon- and iron-ion induced shock waves in DNA duplexes in liquid water. We use the CHARMM force field implemented within the MBN Explorer simulation package to optimize and equilibrate DNA duplexes in liquid water boxes of different sizes and shapes. The translational and vibrational degrees of freedom of water molecules are excited according to the energy deposited by the ions and the subsequent shock waves in liquid water are simulated. The pressure waves generated are studied and compared with an analytical hydrodynamics model which serves as a benchmark for evaluating the suitability of the simulation boxes. The energy deposition in the DNA backbone bonds is also monitored as an estimation of biological damage, something which is not possible with the analytical model. 1 Introduction Collisional phenomena between fast ions and biomolecules is a topic of major interest since it is necessary to understand the mechanisms of such processes if we are to further exploit ion beam cancer therapy (IBCT). In this therapy technique energetic protons or heavier ions are used clinically to treat deeply seated tumors [1]. The Bragg peak is a feature of ion’s propagation in the medium, consisting on a sharp maximum in the depth-dose curve at the end of the incident ions trajectories (contrary to photon or electron beams which have a quite broad energy deposition profile). This feature is advantageous for IBCT from a macroscopic point of view, since energy deposition in the tumor is maximized while surrounding healthy tissue is largely undamaged. However, it is well-known that the effectiveness of IBCT relies on nanoscopic phenomena rather than on macroscopic characteristics [2,3], the former being directly related to atomic collisions with biomolecules. Indeed, a given dose deposited by ions presents a much larger cell killing probability than the same dose deposited by photons. This increased relative biological effectiveness is due  Contribution to the Topical Issue “Atomic Cluster Collisions (7th International Symposium)”, edited by Gerardo Delgado Barrio, Andrey V. Solov’yov, Pablo Villarreal, Rita Prosmiti. a e-mail: b On leave from A. F. Ioffe Physical Technical Institute, 194021 St. Petersburg, Russian Federation. to the large energy deposited around ion tracks on the nanoscale, giving place to an increase in the clustering of damaging events in biomolecules, especially in nuclear DNA, which makes the repair processes less effective [4]. The fundamental aspects of the problem are also of great interest. The irradiation with ions involves new physical phenomena which are not always considered properly (or considered at all) in biophysical models. In fact, the physical and chemical mechanisms underlying IBCT are complex, involving many different space, energy, and time scales, ranging from the transport of energetic ions in macroscopic tissues, the production of secondary electrons and radicals that can propagate on both the nanoand microscale (molecular and cellular levels, respectively) and their interaction with biomolecules on the nanometer scale leading to the final biological outcomes, noticeable in larger space and time scales [3]. More significantly all the physico-chemical processes occurring at the molecular level make it necessary to deviate from a simple energy deposition scheme. On these spatial scales not only energy deposition events are of importance, since the way in which this energy promotes different processes can significantly affect the final effects. While many processes are fairly well-known, such as the electron production and propagation or the generation of free radicals, new interactions are being discovered, such as the dissociative electron attachment, a mechanism by which very low energy electrons (with energies even below the ionization threshold) can fragment biomolecules [5]. Page 2 of 10 In this context another damage mechanism has been theoretically predicted: ion-induced shock waves on the nanometer scale [6–8]. Ion beams can deposit large amounts of energy per unit path length (a carbon ion in the Bragg peak region deposits 900 eV/nm) and the major part of this energy is used to eject secondary electrons of very low energies, below 50 eV [3,9,10]. Most of these secondary electrons transfer their energy to electronic excitations of the medium in less than a nanometer and the time scale over which this energy loss occurs is very short, of a few femtoseconds [11]. These times are very short in comparison with the mechanism capable of dissipating this energy, the electron-phonon coupling, which occurs on the sub-picosecond scale [11]. This situation results in a large heating of the medium in nanocylinders around the ion tracks, providing the conditions for a violent explosion of these “hot cylinders”, a mechanism we refer to as ion-induced shock waves. This shock wave effect was first predicted in terms of a hydrodynamics model where it was shown that pressures up to tens of GPa can be produced around ion tracks [7]. However, even if these high pressures suggest a possibility of biomolecular damage, this information is not sufficient for a detailed quantification, and subsequently molecular dynamics simulations were used to show how these conditions are sufficient to produce bond breaking in nucleosomes [6]. Moreover since the shock waves travel at high velocity they can propagate secondary species (i.e., free radicals, solvated electrons) much faster than the diffusion mechanism. All these dynamical and thermomechanical effects can drastically change the physicochemical environment to which biomolecules are exposed during irradiation. A proper understanding of the characteristics of shock waves requires more systematic studies, especially by the use of molecular dynamics, a technique that can assess their properties and consequences in more detail. Such studies will enhance the understanding of the biological role of ion-induced shock waves, as well as help in the design of possible experiments to verify their existence. In the present paper we report molecular dynamics simulations to study the main features of ion-induced shock waves and their effects (...truncated)