In silico demonstration of in vitro scratch wound healing using PhysiCell.

Objective:

Develop an in silico model that simulates in vitro scratch wound healing cell behavior. We have only one active cell type, the epithelial cells.

• Detect local pressure
• Divide and migrate in low-pressure conditions
• Regain static behavior when pressure increases enough
• Detect velocities of neighboring cells
• Update bias direction based on boids' rule

We also have wall "cells". Static, non-moving, non-proliferating objects that are there to confine the epithelial cells.

For this tool the cells don't need to breathe or eat, they don't die either. We are also not using any kind of chemical signaling/communication. Therefore we disabled the diffusion solver to speed up the simulation.

Boids' movement decision making:

Cell colective motion is achieved with a modified boid's rule,

d (t)= α ^{v (t)}⁄_{|v (t)|} +  β  ^v_n(t)⁄_|vn| + γ b (t - Δt)

b (t) = ^{d (t)}⁄_{|d (t)|}

Where α, β, γ are parameters, v is the cell's velocity, v_n is the sum of the neighbors' velocity and b the bias direction. We define neighbors as all other cells that are in the mechanics' interaction radius of the cell. The self-velocity term can be visualized as a momentum term, the previous bias as a memory of the internal organization of the cell.

1. A Ghaffarizadeh, R Heiland, SH Friedman, SM Mumenthaler, and P Macklin, PhysiCell: an Open Source Physics-Based Cell Simulator for Multicellular Systems, PLoS Comput. Biol. 14(2): e1005991, 2018. DOI: 10.1371/journal.pcbi.1005991   
2. Heiland R, Mishler D, Zhang T, Bower E, Macklin P (2019, in preparation) Xml2jupyter: Mapping parameters between XML and Jupyter Widgets. J Open Source Software.
3. Trepat, Xavier, et al. "Physical forces during collective cell migration." Nature physics 5.6 (2009): 426.
4. Szabo, Balint, et al. "Phase transition in the collective migration of tissue cells: experiment and model." Physical Review E 74.6 (2006): 061908.
5. B. Enyedi and P. Niethammer, "Mechanisms of epithelial wound detection", Trends in Cell Biology, vol. 25, no. 7, pp. 398-407, 2015. Available: 10.1016/j.tcb.2015.02.007 [Accessed 24 April 2019].

Researchers should cite this work as follows:

• Juliano Ferrari Gianlupi, Vedang Narain (2019), "Wound Healing - Physicell," https://nanohub.org/resources/woundhealingpc. (DOI: 10.21981/5FCN-9D81).

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1. Jupyter notebooks
2. nano/bio
3. PhysiCell
4. wound healing
5. xml2jupyter