TY - JOUR
T1 - Ligand accumulation in autocrine cell cultures
AU - Monine, Michael I.
AU - Berezhkovskii, Alexander M.
AU - Joslin, Elizabeth J.
AU - Wiley, H. Steven
AU - Lauffenburger, Douglas A.
AU - Shvartsman, Stanislav Y.
PY - 2005/4
Y1 - 2005/4
N2 - 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-culture 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.
AB - 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-culture 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.
UR - http://www.scopus.com/inward/record.url?scp=22144433647&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=22144433647&partnerID=8YFLogxK
U2 - 10.1529/biophysj.104.051425
DO - 10.1529/biophysj.104.051425
M3 - Article
C2 - 15653719
AN - SCOPUS:22144433647
SN - 0006-3495
VL - 88
SP - 2384
EP - 2390
JO - Biophysical Journal
JF - Biophysical Journal
IS - 4
ER -