Journal of Membrane Science, Vol.139, No.1, 109-124, 1998
A method to evaluate economical carrier-mediated transport across the biological membrane by the optimal control principle
We propose an optimal control strategy for carrier-mediated transport across biological membranes in an attempt to evaluate the functions quantitatively and to create an artificial membrane. The transport system was described by the substrate, unloaded and loaded forms of the carrier where the binding sites were facing to the outside and inside of the membrane with the corresponding control inputs. The temporal behavior of the transport was expressed by a linear four-states model employing the conservation law. We assigned the state variables for the concentrations of the loaded and unloaded carriers on both sides of the unit membrane area. Two control inputs were set on each individual state variable so as to describe the producing and converting processes. The cost function to evaluate the performance of the transport involved the temporal static concentration changes in the loaded and unloaded carriers and the control inputs for driving the system. Minimizing this cost function resulted in a smooth and non wasteful transport with the least energy consumption. The relative magnitude of minimizing these quantities was characterized by the weighting coefficients and we defined that the optimal transport state is achieved when this cost function has been minimized. We utilized reported experimental data of Na/glucose cotransport for the initial condition and rate constants. Since transport by the carrier is a recycling process, we set a rigorous terminal condition as the target state for the optimally controlled transport. The optimized system equations and co-state equations were solved numerically as a multiple points boundary value problem. The influences of a given weighting coefficient were observed not only on the time course of its proper variable but extended to those of other variables, The changes in the time course could be explained by the compensatory action of the optimized control input so as to prevent excessive increase or decrease of the materials. Finally we showed the successful simulation of experimental data by the present method. The present method is available for evaluating the function of biological transport and for creating an artificial membrane.
Keywords:ELECTROGENIC PROPERTIES;SMOOTH-MUSCLE;CA-2+ PUMP;PHOSPHATIDYLINOSITOL;PHOSPHORYLATION;COTRANSPORTER;CHANNEL;ATPASE