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Computer simulations of cell-target encounter including biased cell motion toward targets: single and multiple
S B Charnick1, E S Fisher, D A Lauffenburger
1Department of Chemical Engineering, University of Pennsylvania, Philadelphia 19104-6393.
Insights
Chemotaxis, the directed movement of immune cells, significantly speeds up target encounters. Even a small chemotactic bias dramatically reduces cell-target meeting times, crucial for tissue clearance.
Area of Science:
- Computational Biology
- Immunology
- Cellular Dynamics
Background:
- Immune cell function, such as infectious agent clearance, relies on encountering targets within tissues.
- This encounter process is frequently the rate-limiting step in immune responses.
- Chemotaxis, or directed cell movement, is a known mechanism to enhance cell-target encounters.
Purpose of the Study:
- To simulate discrete cell-target encounter events in two dimensions.
- To verify predictions from continuum models regarding the impact of chemotaxis on encounter rates.
- To investigate the influence of chemotactic bias on encounter times and target clearance kinetics.
Main Methods:
- Development of computer simulations for discrete cell-target encounter events in 2D.
- Simulation of scenarios with single cell-target pairs and multiple cell-target populations.
- Analysis of encounter times and dynamics under varying degrees of chemotactic bias.
Main Results:
- Simulations confirm that a small chemotactic bias dramatically decreases cell-target encounter time.
- Further increases in chemotactic bias yield diminishing returns in reducing encounter time.
- Chemotactic ability is a key factor in target clearance kinetics, dependent on initial cell-target ratios and distributions.
Conclusions:
- Computer simulations validate the significant advantage of chemotaxis in increasing cell-target encounter rates.
- Chemotaxis plays a critical role in the efficiency of immune cell functions and target clearance.
- This study presents novel simulations of biased particle-target encounters, with broad applicability.
Abstract:
In order for immune cells to carry out many of their functions, including clearance of infectious agents from tissue, they must first encounter their targets in the tissue. This encounter process is often the rate-limiting step in the overall function. Most immune cells exhibit chemotactic ability, and previous continuum models for encounter rates and dynamics have shown that chemotaxis can be a great advantage to cells by greatly increasing encounter rates relative to those for randomly moving cells. This paper describes computer simulations of discrete cell-target encounter events in two dimensions, for the two cases considered by the continuum models: where only a single cell and a single target are present, and where many cells and targets are present. The results of these simulations verify our previous model predictions that a small amount of chemotactic bias dramatically decreases the encounter time, while further increases in the amount of bias have a much smaller effect. Chemotactic ability is shown to be an important determinant of the kinetics of target clearance, and its effects depend on the initial cell-target ratio and the initial distributions of cells and targets. To the best of our knowledge, this work provides the first computer simulations of particle-target encounter in which there is biased motion of particles toward their targets, and is therefore of general interest beyond specific application to immune cell function.
