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Biophys. J. BioFAST: First Published January 14, 2005. doi:10.1529/biophysj.104.051425
© 2005 by the Biophysical Society.

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BIOPHYSICAL THEORY AND MODELING

Ligand accumulation in autocrine cell cultures

Michael M Monine 1, Alexander M Berezhkovskii 2, Elizabeth J Joslin 3, H Steven Wiley 4, Douglas A Lauffenburger 5 and Stanislav Y Shvartsman 6*

1 Department of Chemical Engineering, Princeton University
2 Center for Information Technology, National Institutes of Health
3 MIT
4 Biological Sciences Division, Pacific Northwest National Laboratory
5 Biological Engineering Division, MIT
6 Dep. of Chemical Engineering and Lewis-Sigler Institute for Integrative Genomics, Princeton Un.

* To whom correspondence should be addressed. E-mail: stas{at}princeton.edu.

Submitted on August 23, 2004
Revised on October 6, 2004
Accepted on 4 January 2005


  Abstract
Cell culture assays are routinely used to analyze autocrine signaling systems, but quantitative experiments are rarely possible. To enable the quantitative design and analysis of experiments with autocrine cells, we develop a biophysical theory of ligand accumulation in cell cultures assays. Our theory predicts the ligand concentration as a function of time and measurable parameters of autocrine cells and cell culture experiments. The key step of our analysis is the derivation of the survival probability of a single ligand released from the surface of an autocrine cell. An expression for this probability is derived using the boundary homogenization approach and tested by stochastic simulations. We use this expression in the integral balance equations, from which we find the Laplace transform of the ligand concentration. We demonstrate how the theory works by analyzing the autocrine epidermal growth factor receptor system and discuss the extension of our methods to other experiments with cultured autocrine cells.

Key Words: autocrine, cell culture, homogenization, multiscale, receptor, stochastic




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Copyright © 2005 by the Biophysical Society.