Figure 10.

Evidence that GARD is inherently an out-of-equilibrium model. In the main figure, the time dependence of the molar fraction n_i/N inside a GARD assembly is shown for each of the molecule types A_i (different colours), as a function of time (units are intervals of 0.05 s of simulated time along a dynamic progression of the equation in figure 1). This simulation, unlike the more standard ones, takes place without fission and with a finite supply of molecules. In the early part of the time course, transient composome-like dynamics takes place, as evidenced by the differential molar fractions of certain molecule types. At later times, due to exhausted resources, all molecular species assume an identical molar fraction plateau, reaching equilibrium. Concentration equality at the plateau is expected, because in our simulations all external molecular concentrations are set as equal, and all thermodynamic constants (K_i = k_i/k_−i, see equation in figure 1) are also set to be equal. By contrast, the transient is clearly out of equilibrium, as is the case for the exact same simulation conducted with fission and with unlimited compound supply [54]. Bottom: gradually increasing assembly size, reaching a plateau upon amphiphile depletion, where equilibrium is attained. Inset: Free energy diagram for assembly entry and exit of an individual amphiphile. The entry is associated with a negative equilibrium free energy change (ΔG, measuring approx. 20 kCal mol⁻¹, [140]). The free energy of activation (ΔG^ǂ) barrier may have to do with the obligatory unfavourable contact of the hydrophobic tail of a half-inserted amphiphile with the polar headgroups of molecules already within the assembly [140]. Figure is modified from [54].