Second, systems that were simulated under neutral conditions (pH ≈ pKa) show that, in most simulations, the mRNA payloads incorporated (Figure ) into the ionizable lipids in either bilayers or tubular structures. The assimilation of mRNA and lipids can be a relevant mechanism for the payload stabilization from RNase degradation, which could be one factor that ultimately helps increase mRNA stability and transfection efficiency associated with reported manufacturing methods. Finally, to simulate the effects of dialyzing an LNP with bleb structures in a neutral pH buffered environment, as described in the literature, the self-assembly structure of DODAP generated in acidic conditions was simulated for 500 ns at pH = 7.4 (n = 3, Figure ). Within ~200 ns of simulation time, the mesoporous structure collapsed to form a bilayer and incorporated the payload within the lipids to form an aggregate structure identical to those observed for self-assembly simulations at neutral pH environments. This spontaneous restructuring of the mesoporous LNP structures into mRNA-incorporated bilayers observed in silico demonstrates that self-assembled structures formed in simulated acidic environments can readily undergo pHdependent structural transitions. Furthermore, these computational results also indicate that such relatively large structural transitions are feasible for real LNP systems, further emphasizing the sensitivity of the conformation of the LNP interior to the pH of the solution.