3D multicellular model of shock wave-cell interaction.

Understanding the interaction between shock waves and tissue is critical for advancing the use of shock waves for medical applications, such as cancer therapy. This work aims to study shock wave-cell interaction in a more realistic environment, relevant to in vitro and in vivo studies, by using 3D computational models of healthy and cancerous cells. The results indicate that for a single cell embedded in an extracellular environment, the cellular geometry does not influence significantly the membrane strain but does influence the von Mises stress. On the contrary, the presence of neighbouring cells has a strong effect on the cell response, by increasing fourfold both quantities. The membrane strain response of a cell converges with more than three neighbouring cell layers, indicating that a cluster of four layers of cells is sufficient to model the membrane strain in a large domain of tissue. However, a full 3D tissue model is needed if the stress evaluation is of main interest. A tumour mimicking multicellular spheroid model is also proposed to study mutual interaction between healthy and cancer cells and shows that cancer cells can be specifically targeted in an early stage tumour-mimicking environment.

STATEMENT OF SIGNIFICANCE: This work presents 3D computational models of shock-wave/cell interaction in a biophysically realistic environment using real cell morphology in tissue-mimicking phantoms and multicellular spheroids. Results show that cell morphology does not strongly influence the membrane strain but influences the von Mises stress. While the presence of neighbouring cells significantly increases the cell response, four cell layers are enough to capture the membrane strain change in tissue. However, a full tissue model is necessary if accurate stress analysis is needed. The work also shows that cancer cells can be specifically targeted in early stage tumour mimicking environment. This work is a step towards realistic modelling of shock-wave/cell interactions in tissues and provides insight on the use of 3D models for different scenarios.