Research Day ‘06
A Computational Model of Chemotaxis-Based Cell Aggregation
M. Eyiyurekli, P. I. Lelkes, D. E. Breen
 
Abstract
 
Chemotaxis (CTX) is the phenomenon where cells detect gradients of chemicals (chemoattractants) and respond to the chemical stimulus by moving according to these chemical gradients, either towards (positive CTX) or away (negative CRX) from the source. Multicellular aggregates and eventually tissue-like assemblies are formed when individual cells attach to other cells. Understanding the influence of the many components of CTX on overall cell aggregation should lead to a more detailed understanding of cellular aggregation and organogenesis, and also facilitate the development of novel technologies for tissue engineering based on controlling or directing these underlying biological processes. We have created a 2D computational model that is capable of simulating CTX-based cell aggregation. Our model attempts to capture the characteristics of cell behavior that are most important for cell aggregation. In our simulations each cell is defined by a collection of parameters and actions, such as the number and the position of CTX receptors on the cell surface, location of the cell, age, life cycle stage, chemoattractant emission rate, diffusion radius, proliferation rate and number of attached cells. Our virtual cells are able to emit chemoattractants, sense the chemoattractant gradient, move in the direction of the gradient, proliferate, adhere to other cells, age and die. The calculations are validated by a close fit to actual cell-cell aggregation data obtained from 24-hour studies of HepG2 hepatocytes. The initial results of our simulations demonstrate that our model is capable of producing cell aggregation distributions similar to those found in live cell experiments.
 
 
Master’s Thesis August ’06
A Computational Model of Chemotaxis-Based Cell Aggregation
Manolya Eyiyurekli
 
Abstract
 
We present a 2D computational model that successfully captures the cell be-
haviors that play important roles in cell aggregation. A virtual cell in our model is
designed as an independent, discrete unit with a collection of parameters and actions.
Each cell is defined by its location, number and position of receptors, chemoattrac-
tant emission and response rates, age, life cycle stage, proliferation rate and number
of attached cells. All cells are capable of emitting and sensing chemoattractant
chemical, moving, attaching to other cells, dividing, aging and dying.
We validate and fine-tune our model by comparing simulated 24-hour aggregation
experiments with data derived from in vitro PC12 cell experiments. Quantitative
comparisons of the aggregate size distributions from the two experiments are pro-
duced using the Earth Mover’s Distance (EMD) metric. We compare the two size
distributions produced after 24 hours of in vitro cell aggregation and the equivalent
computer simulated process. Iteratively modifying the model’s parameter values
and measuring the difference between the in silico and and in vitro results allow
us to determine the optimal values that produce simulated aggregation outcomes
closely matched to the PC12 experiments. Simulation results confirm the ability of
the model to recreate large-scale aggregation behaviors seen in live cell experiments.
Through simulation studies important factors affecting cell aggregation, such
as a cell’s proliferation rate, response rate to chemoattractant gradient, length of the quiescent stage after cell division and up/down-regulation of chemoattractant
emission based on the number of attached cells, are identified.
 
 
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