A systematic approach for developing mechanistic models for realistic simulation of cancer cell motion and deformation

Pouyan Keshavarz Motamed,Nima Maftoon

doi:10.1038/s41598-021-00905-3

Abstract

Understanding and predicting metastatic progression and developing novel diagnostic methods can highly benefit from accurate models of the deformability of cancer cells. Spring-based network models of cells can provide a versatile way of integrating deforming cancer cells with other physical and biochemical phenomena, but these models have parameters that need to be accurately identified. In this study we established a systematic method for identifying parameters of spring-network models of cancer cells. We developed a genetic algorithm and coupled it to the fluid–solid interaction model of the cell, immersed in blood plasma or other fluids, to minimize the difference between numerical and experimental data of cell motion and deformation. We used the method to create a validated model for the human lung cancer cell line (H1975), employing existing experimental data of its deformation in a narrow microchannel constriction considering cell-wall friction. Furthermore, using this validated model with accurately identified parameters, we studied the details of motion and deformation of the cancer cell in the microchannel constriction and the effects of flow rates on them. We found that ignoring the viscosity of the cell membrane and the friction between the cell and wall can introduce remarkable errors.

Highlights

Understanding and predicting metastatic progression and developing novel diagnostic methods can highly benefit from accurate models of the deformability of cancer cells
The cancer cells that intravasate and enter the bloodstream are known as circulating tumor cells (CTCs)
The deformability of CTCs plays an important role in the metastasis cascade because entrapment of CTCs in capillaries and their penetration into the endothelial cell–cell junctions during intravasation and extravasation highly depend on their drastic deformation[2]

Summary

Introduction

Understanding and predicting metastatic progression and developing novel diagnostic methods can highly benefit from accurate models of the deformability of cancer cells. We used the method to create a validated model for the human lung cancer cell line (H1975), employing existing experimental data of its deformation in a narrow microchannel constriction considering cell-wall friction. Using this validated model with accurately identified parameters, we studied the details of motion and deformation of the cancer cell in the microchannel constriction and the effects of flow rates on them. Developing novel diagnostic tools and novel tools for predicting metastatic spreading requires accurate quantitative models of cell deformability Such models require experimental data of cancer cell deformation as well as highly efficient computational methods in terms of calculation time. Expensive for modelling deformations of cells in interaction with the surrounding fluid domain and the liquid drop models are insufficient in simulating cell transit in the constriction since they assume a lubrication layer between the cell and the constriction w alls[14]

Objectives

Methods

Results

Conclusion