Modeling Living Cells Within Microfluidic Systems Using Cellular Automata Models

Julia Ballesteros Hernando,Milagros Ramos Gómez,Andrés Díaz Lantada

doi:10.1038/s41598-019-51494-1

Julia Ballesteros Hernando, Milagros Ramos Gómez + Show 1 more

Open Access

https://doi.org/10.1038/s41598-019-51494-1

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Abstract

Several computational models, both continuum and discrete, allow for the simulation of collective cell behaviors in connection with challenges linked to disease modeling and understanding. Normally, discrete cell modelling employs quasi-infinite or boundary-less 2D lattices, hence modeling collective cell behaviors in Petri dish-like environments. The advent of lab- and organ-on-a-chip devices proves that the information obtained from 2D cell cultures, upon Petri dishes, differs importantly from the results obtained in more biomimetic micro-fluidic environments, made of interconnected chambers and channels. However, discrete cell modelling within lab- and organ-on-a-chip devices, to our knowledge, is not yet found in the literature, although it may prove useful for designing and optimizing these types of systems. Consequently, in this study we focus on the establishment of a direct connection between the computer-aided designs (CAD) of microfluidic systems, especially labs- and organs-on-chips (and their multi-chamber and multi-channel structures), and the lattices for discrete cell modeling approaches aimed at the simulation of collective cell interactions, whose boundaries are defined directly from the CAD models. We illustrate the proposal using a quite straightforward cellular automata model, apply it to simulating cells with different growth rates, within a selected set of microsystem designs, and validate it by tuning the growth rates with the support of cell culture experiments and by checking the results with a real microfluidic system.

Highlights

Recent progresses in the design, prototyping and manufacturing of microfluidic systems[1,2] have enabled new ways to approach the study of disease, with the advent of lab-on-a-chip technologies that integrate several lab operations in single microfluidic networks, and to advance in the comprehension of cell-cell and cell-material interactions, with the engineering of organ-on-a-chip (O-o-C) devices that mimic the physiological response of entire organs and systems by employing multi-channel cell culture chips[3,4]
In this study we focus on the establishment of a direct connection between the computer-aided designs (CAD) of microfluidic systems, especially labs- and organs-on-chips, and the lattices for discrete cell modelling approaches aimed at the simulation of collective cell interactions, whose boundaries are defined directly from the CAD models
Throughout the study we use NX-8.5 (Siemens PLM Solutions) for computer-aided design purposes –mainly for designing the microfluidic systems and organ-on-a-chip devices– and Matlab (The Mathworks Inc.) for developing the code of the cellular automata model working upon such microsystems and performing the collective cell simulations

Summary

Introduction

Recent progresses in the design, prototyping and manufacturing of microfluidic systems[1,2] have enabled new ways to approach the study of disease, with the advent of lab-on-a-chip technologies that integrate several lab operations in single microfluidic networks, and to advance in the comprehension of cell-cell and cell-material interactions, with the engineering of organ-on-a-chip (O-o-C) devices that mimic the physiological response of entire organs and systems by employing multi-channel cell culture chips[3,4] These models are starting to replace more common cell culture systems, mainly Petri dishes, as the multi-channel structure provides cells with a 2D1/2 or 3D environment more similar to the actual in vivo configurations. Apart from the initial game-like demonstrations, further studies led to verifying that extremely complex systems could be modeled by using cellular automata[15]

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