Goal is to build a simple cell based on a replication vesicle for compartmentalization and a replicating genome. If the cell is to be simple, the environment must be correspondingly complex. Here are some technical considerations relevant to the construction of such a protocell:
- No biochemical machinery - all processes must be spontaneous
- nucleic acid template-directed copying, strand separation
- membrane dynamics: growth, division, permeability
Fatty acid structures can actually self-organize into liposomes given particular environmental conditions. At a pH greater than 10, myristoleate will from into single layer micelles. There is a threshold at a lower pH at which this micelles reorganize into double-layered vesicles.
Additionally, osmotic pressures can be manipulated to drive membrane growth. This presents a spontaneous, downhill pathway for building vesicles.
Thirdly, larger vesicles can be divided into smaller vesicles by forcing it through solid channel smaller in width than the vesicle.
nucleic acid replication:
Need more energy to make the rate of the spontaneous polymerization reaction faster. How? Make ATP portion of the nucleotides more reactive: mess with the nucleobases, change the leaving groups, practically anything. Changing the nucleophile seems most promising, i.e. changing the organization sugar backbone.
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Over two days, without an enzyme, one can extend a primer naturally...
Phosphoramidate DNA, ending not with a 3'OH, but with a 3'amidazolide[?] group.
Interestingly, MA:GMM vesicles are stable up to 90+ degrees C, and additionally nucleotide permeability goes up, facilitating nucleic acid separation and replication.
So, the experiment everyone has wanted to do for years: can we add nucleotides to the outside of such a vesicle containing a prebuilt primer, watch them diffuse in, and then polymerize? Yes! In an elementary manner, at least.