Retroactivity Attenuation in Bio-Molecular Systems Based on Timescale Separation

As with several engineering systems, bio-molecular systems display impedance-like effects at interconnections, called retroactivity. In this paper, we propose a mechanism that exploits the natural timescale separation present in bio-molecular systems to attenuate retroactivity. Retroactivity enters the dynamics of a bio-molecular system as a state dependent disturbance multiplied by gains that can be very large. By virtue of the system structure, retroactivity can be arbitrarily attenuated by internal system gains even when these are much smaller than the gains multiplying retroactivity terms. This result is obtained by employing a suitable change of coordinates and a nested application of the singular perturbation theorem on the finite time interval. As an application example, we show that two modules extracted from natural signal transduction pathways have a remarkable capability of attenuating retroactivity, which is certainly desirable in any (engineered or natural) signal transmission system.