A Dynamical Model of Oncotripsy by Mechanical Cell Fatigue: Selective Cancer Cell Ablation by Low-Intensity Pulsed Ultrasound (LIPUS)

TL;DR

This paper develops a dynamical model of oncotripsy using cell mechanics and statistical theories to explain selective cancer cell ablation by low-intensity pulsed ultrasound, aiding understanding and optimization.

Contribution

It introduces a new dynamical model combining cell mechanics and damage-repair processes to explain oncotripsy effects and supports process optimization.

Findings

Model predicts cell-death dependence on parameters.

Provides conceptual understanding of oncotripsy.

Supports data trends in cell ablation studies.

Abstract

The method of oncotripsy, first proposed in [S. Heyden and M. Ortiz (2016). Oncotripsy: Targeting cancer cells selectively via resonant harmonic excitation. Journal of the Mechanics and Physics of Solids, 92:164-175], exploits aberrations in the material properties and morphology of cancerous cells in order to ablate them selectively by means of tuned low-intensity pulsed ultrasound (LIPUS). We propose a dynamical model of oncotripsy that follows as an application of cell dynamics, statistical mechanical theory of network elasticity and 'birth-death' kinetics to describe processes of damage and repair of the cytoskeleton. We also develop a reduced dynamical model that approximates the three-dimensional dynamics of the cell and facilitates parametric studies, including sensitivity analysis and process optimization. We show that the dynamical model predicts---and provides a conceptual basis for understanding---the oncotripsy effect and other trends in the data of [D. R. Mittelstein, J. Ye, E. F. Schibber, A. Roychoudhury, L. T. Martinez, M. H. Fekrazad, M. Ortiz, P. P. Lee, M. G. Shapiro, M. Gharib (2019). Selective Ablation of Cancer Cells with Low Intensity Pulsed Ultrasound. BioRxiv] for cells in suspension, including the dependence of cell-death curves on cell and process parameters.