Mathematical modeling of marker influx and efflux in cells |
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Authors: | C A Heckman C S Runyeon J G Wade S Seubert |
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Institution: | (1) Department of Biological Sciences, Bowling Green State University, Bowling Green, OH 43403-0212, USA;(2) Department of Mathematics and Statistics, Bowling Green State University, Bowling Green, OH 43403-0221, USA |
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Abstract: | The tumor promoter, phorbol 12-myristate 13-acetate (PMA), affects the processing of fluid that enters a cell from the ambient
medium. Previous work showed that marker accumulates to a higher level in PMA-treated than in untreated cells. Since PMA also
affects the physical activity of the membrane and stimulates the normal process of taking up extracellular fluid, called endocytosis,
it is important to learn whether the perturbations in fluid processing can be attributed entirely to a change in the cell’s
limiting membrane. To this end, a model for fluid uptake and processing was developed and applied to experiments in which
a marker for extracellular fluid was added to cells. From previous work on marker accumulation, it was deduced that there
were at least two functional compartments involved in fluid movement. Compartment I is a rapidly filling and rapidly recycling
compartment. Compartment II is a slowly filling and emptying compartment. Three routes of vesicle traffic must be considered,
one mediating influx from the ambient medium into compartment I, a second, efflux from compartment I to the medium, and a
third efflux from compartment I into compartment II. Using earlier models for processing, workers found it difficult to estimate
rates of movement through either of the latter routes, as well as the volume of compartment I. The difficulty arises from
the fact that only one kinetic constant can be estimated directly from data, namely the instantaneous uptake rate. The remaining
data depend on measuring the total mass of marker in the cells. Since the concentration of marker in the cell changes continuously,
it is advantageous to employ differential equations to simulate the tracer movement. By applying the model to experimental
values, we found estimates for all three rates of fluid movement and the volume of compartment I. It is thought that the model
will enable us to determine whether apparent alterations in the time course of uptake arise solely from altered properties
of the limiting membrane.
This revised version submitted December, 2000. Research supported in part by a grant from the National Institutes of Health,
R15 CA78322-01. |
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