Molecular dynamics cell membrane modeling: Application to ultrasound cancer treatment

Abstract

The application of ultrasound and pulsed lasers to biological tissues is a more and more promising cancer treatment method; due to its capability of retarding a tumor growth, either alone or by increasing the uptake of anticancer agents through the cell membrane, hence, enhancing the efficiency of chemotherapy. Although its computational cost, the Molecular Dynamics numerical method is key for fully capture the physics of the processes involved when the shock wave generated interacts with the biological membrane. In order to eliminate free-surface effects, molecular-level modeling of shocks is typically carried out using computational systems with periodic boundary conditions, limiting the total simulation time to the one it takes for the shock to cross the domain. Nevertheless, regarding the ultrasound cancer treatment, the analysis of the effect of the shock wave in the long-time scale is of vital importance to ensure that the diffusivity is increased only temporally. Furthermore, coarse graining studies posit that there is a critical impulse beyond which the structural recovery from the induced damage is no longer produced, but a slow diffusive disintegration of the membrane. In the present research thesis, a novel method that allows capturing both the ini- tial shock transit as well as the subsequent longer-time-scale has been developed, validated against the experimental and numerical data available for 1,2-dipalmitoyl- sn-phosphatidylcholine lipid bilayers and verified though convergence studies. It is based on surrounding the system by symmetric ones in the longitudinal direction, achieving the fact that the 98% of the shock wave impulse is cancelled out when the end of the domain is reached. For impulses > 0.45mP a · s no self-recovery of the bilayer is observed whereas for impulses < 0.3mPa·s, the increase of the transversal diffusivity of the lipids (ballistic motion), and consequent enhancement of drug absorption across the membrane, is followed by a progressive recovery of the initial values.