Harold Fellermann, Steen Rasmussen, Ricard Solé, Hans Ziock

Paper #: 06-12-050

Cross-reactions and other systematic issues generated by the coupling of functional chemical subsystems pose the largest challenge for assembling a viable protocell in the laboratory. Our current work seeks to identify and clarify such key issues as we represent and analyze in simulation a full implementation of a minimal protocell. Using a 3D dissipative particle dynamics (DPD) simulation method we are able to address the coupled diffusion, self-assembly, and chemical reaction processes, required to model a full life cycle of the protocell, the protocell being composed of coupled genetic, metabolic, and container subsystems. Utilizing this minimal structural and functional representation of the constituent molecules, their interactions, and their reactions, we identify and explore the nature of the many linked processes for the full protocellular system. Obviously the simplicity of this simulation method combined with the inherent system complexity prevents us from expecting quantitative simulation predictions from these investigations. However, we report important findings on systemic processes, some previously predicted, and some newly discovered, as we couple the protocellular self-assembly processes and chemical reactions. For example, our simulations indicate that the container stability is significantly affected by the amount of oily precursor lipids and sensitizers and affect the partition of molecules in the container division process. Also a continuous supply of oily lipid precursors to the protocell environment at a very slow rate will pulse the protocellular loading (feeding) as oil blobs will form in water and whole blobs will be absorbed at one time. By orchestrating the precursor injection rate compared to diffusion, precursor self-assembly, protocell concentration, etc., an optimal size resource package can be spontaneously generated. Replication of the amphiphilic genes is better on the surface of a micelle with a substantial oil core (loaded micelle) than on a regular micelle due to the higher aggregate stability. Also replication of amphiphilic genes (genes with lipophilic backbones) in bulk water can be inhibited due to their tendency to form aggregates. Further the template directed gene ligation rate depends not only on the component monomers but also on the sequence of these monomers in the template.