Understanding the thermodynamics of the duplication process is a fundamental step towards a comprehensive physical theory of biological systems. However, the immense complexity of real cells obscures the fundamental tensions between energy gradients and entropic contributions that underlie duplication. The study of synthetic, feasible systems reproducing part of the key ingredients of living entities but overcoming major sources of biological complexity is of great relevance to deepen the comprehension of the fundamental thermodynamic processes underlying life and its prevalence. In this paper an abstract—yet realistic—synthetic system made of small synthetic protocell aggregates is studied in detail. A fundamental relation between free energy and entropic gradients is derived for a general, non-equilibrium scenario, setting the thermodynamic conditions for the occurrence and prevalence of duplication phenomena. This relation sets explicitly how the energy gradients invested in creating and maintaining structural—and eventually, functional—elements of the system must always compensate the entropic gradients, whose contributions come from changes in the translational, configurational, and macrostate entropies, as well as from dissipation due to irreversible transitions. Work/energy relations are also derived, defining lower bounds on the energy required for the duplication event to take place. A specific example including real ternary emulsions is provided in order to grasp the orders of magnitude involved in the problem. It is found that the minimal work invested over the system to trigger a duplication event is around ~
, which results, in the case of duplication of all the vesicles contained in a liter of emulsion, in an amount of energy around ~
. Without aiming to describe a truly biological process of duplication, this theoretical contribution seeks to explicitly define and identify the key actors that participate in it.
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