An in-silico study of cancer cell survival and spatial distribution within a 3D microenvironment

Marilisa Cortesi,Chiara Liverani,Emanuele Giordano,Toni Ibrahim,Laura Mercatali

doi:10.1038/s41598-020-69862-7

Abstract

3D cell cultures are in-vitro models representing a significant improvement with respect to traditional monolayers. Their diffusion and applicability, however, are hampered by the complexity of 3D systems, that add new physical variables for experimental analyses. In order to account for these additional features and improve the study of 3D cultures, we here present SALSA (ScAffoLd SimulAtor), a general purpose computational tool that can simulate the behavior of a population of cells cultured in a 3D scaffold. This software allows for the complete customization of both the polymeric template structure and the cell population behavior and characteristics. In the following the technical description of SALSA will be presented, together with its validation and an example of how it could be used to optimize the experimental analysis of two breast cancer cell lines cultured in collagen scaffolds. This work contributes to the growing field of integrated in-silico/in-vitro analysis of biological systems, which have great potential for the study of complex cell population behaviours and could lead to improve and facilitate the effectiveness and diffusion of 3D cell culture models.

Highlights

Cell culture is currently experiencing a fundamental shift from traditional 2D to 3D systems, that are more realistic representations of a biological tissue
To integrate this important functionality we developed a general purpose scaffold simulator named SALSA that can be programmed to reproduce the behaviour of a population of arbitrary cells, grown in 3D scaffolds of tunable size and material
The validation of SALSA consisted in comparing, over time, a) the cell density measured in-vitro to the results obtained with the in-silico simulation, and b) the ability of the virtual cells of inducing a stiffening of the extracellular matrix (ECM) comparable to what observed experimentally

Summary

Introduction

Cell culture is currently experiencing a fundamental shift from traditional 2D to 3D systems, that are more realistic representations of a biological tissue. As an example there are multiple models describing cancer-related cellular processes[10,11,12,13,14,15,16,17] and the effect of antineoplastic therapies[18,19,20,21,22,23,24] but most of them are presented as theoretical frameworks that do not aim at driving the experimental activity To integrate this important functionality we developed a general purpose scaffold simulator named SALSA that can be programmed to reproduce the behaviour of a population of arbitrary cells, grown in 3D scaffolds of tunable size and material. This choice effectively realizes a simplified finite element / agent based combined m odel[30,31,32] that allows for the representation of the main features of the in-vitro setup while limiting the computational cost

Methods

Results

Conclusion