Signal transduction inside and across the cells, also called cellular signaling, is key to most biological functions and is ultimately related with both life and death of the organisms. The processes giving rise to the propagation of biosignals are complex and extremely cooperative and occur in a far-from thermodynamic equilibrium regime. They are also driven by activation kinetics strongly dependent on local energetics. For these reasons, a nonequilibrium thermodynamical description, taking into account not just the activation of second messengers, but also transport processes and dissipation is desirable. Here we present a proposal for such a formalism, that considers cells as small thermodynamical systems and incorporates the role of fluctuations as intrinsic to the dynamics in a spirit guided by mesoscopic nonequilibrium thermodynamics. We present also a minimal model for cellular signaling that includes contributions from activation, transport, and intrinsic fluctuations. We finally illustrate its feasibility by considering the case of FAS signaling which is a vital signal transduction pathway that determines either cell survival or death by apoptosis. 1. Introduction Survival of living organisms is intimately linked to their ability to react quite efficiently to even extremely weak external signals. Common examples are the reaction of the human eye to single light photons [1, 2], the reaction of a male butterfly to a single pheromone molecule coming from a female at a distance that sometimes is in the order of kilometers [3], and so forth. Cellular receptors react to hormones, cytokines, or antigens at very low concentrations. This strong reaction to a weak impulse is attained by an amplification process which is performed by means of special pathways of free energy transduction. Mechanisms such as immune system response, thermal-shock inhibitions, and cardiovascular rearrangement in response to environmental changes are all mediated by signaling processes. Signal transduction (information flow) is, thus, equally important, if not more important, for the functioning of a living organisms than metabolism and energy flow. Signal transduction or cell signaling is the generic name of the set of concatenated processes or stages in which a cell transforms a certain signal or stimulus—either intercellular or intracellular—into another signal or a specific response. Cell signaling affects the complex arrangement of biochemical reactions inside the cell that takes place by means of enzymes that are bounded to other molecules called second messengers. Each
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