INTERNAL REGULATION OF A MODULAR SYSTEM - THE DIFFERENT FACES OF INTERNAL CONTROL

The living cell houses a multitude of molecular processes that operate simultaneously in a mutually consistent fashion. A certain degree of organization stands out, e.g. in terms of the various metabolic pathwa ys, transcription versus translation, signal transduction versus metab olism. This paper shows that by taking one of the aforementioned organ izational principles into account, the complexity of understanding cel l function quantitatively may be reduced significantly. To this aim th e definition of the corresponding type of organization is refined and the conceptual tools used in the analysis of the control of cell funct ion are adjusted. The approach is elaborated for a theoretical model o f cell function, in which the latter depends on a constellation of int erdependent but unconnected modules. The organization of a system is r educed to global control within a limited set of partaking modules and the links between them. Information about the systems total internal control and regulability is then drastically reduced to the informatio n specifying global control and the regulability of the pathways that constitute the system. It is shown quantitatively how control at a low er level of organization bears on the control of the cell as a whole. The approach centers on writing the product of control (matrix) and el asticity (matrix) at a number of different levels of aggregation; thes e products equalling the identity (matrix) under different conditions. We demonstrate that there are at least three ways in which control an d regulability of a system can be matched. In one, the true control wi thin and between the modules of the systems is the inverse of the prim ary regulability (i.e. elasticity plus stoichiometry). In a second, th e control internal to a module (but partly determined through the othe r modules) is matched by the inverse of newly defined 'global' regulab ilities for each module separately, which comprise the regulatory impa ct of the remainder of the system. In the third, the regulabilities ar e the ones intrinsic to the module and the control is taken equal to t he control that would reign in the absence of the regulatory interacti ons between the units. In making these distinctions, it becomes transp arent how much control stems from control within the organizational mo dules, and how much derives from the regulatory interactions between t hem. Control through other modules turns out to be equivalent, al stea dy state, to control within a module. The implications of this type of cellular organization for the location of the steady-state operating point is discussed. (C) 1997 Elsevier Science Ireland Ltd.