Cis-Action

No Translation Necessary

"Towards the design and synthesis of an artificial cell" - Jack Szostak

First point: “I really don’t think this has any practical applications, at least in the foreseeable future.”

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

Building the membrane:
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.

[get more details about this]
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.

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