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Peptide–nucleotide microdroplets as a step towards a membrane-free protocell model


Although phospholipid bilayers are ubiquitous in modern cells, their impermeability, lack of dynamic properties, and synthetic complexity are difficult to reconcile with plausible pathways of proto-metabolism, growth and division. Here, we present an alternative membrane-free model, which demonstrates that low-molecular-weight mononucleotides and simple cationic peptides spontaneously accumulate in water into microdroplets that are stable to changes in temperature and salt concentration, undergo pH-induced cycles of growth and decay, and promote α-helical peptide secondary structure. Moreover, the microdroplets selectively sequester porphyrins, inorganic nanoparticles and enzymes to generate supramolecular stacked arrays of light-harvesting molecules, nanoparticle-mediated oxidase activity, and enhanced rates of glucose phosphorylation, respectively. Taken together, our results suggest that peptide–nucleotide microdroplets can be considered as a new type of protocell model that could be used to develop novel bioreactors, primitive artificial cells and plausible pathways to prebiotic organization before the emergence of lipid-based compartmentalization on the early Earth.

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Figure 1: Formation of peptide–nucleotide membrane-free microcompartments.
Figure 2: Structure and properties of peptide–nucleotide droplets.
Figure 3: Nanoparticle uptake and catalytic reactions in peptide–nucleotide droplets.


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The authors thank the Engineering and Physical Sciences Research Council for financial support to D.S.W. and A.W.P. (Cross-disciplinary Interfaces Fellowship) and Mitsubishi Chemical Corporation for partial funding for S.K. The authors also thank C.R.C. Hak for help with optical imaging, D. Walsh for assistance with nanoparticle preparations and A.J. Patil for discussions.

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S.M. conceived the project and wrote the final paper. S.K., D.S.W. and A.W.P. designed the experiments. S.K. and D.S.W. performed the experiments and wrote initial drafts of the work. All authors discussed the results and commented on the manuscript.

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Correspondence to Stephen Mann.

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The authors declare no competing financial interests.

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Koga, S., Williams, D., Perriman, A. et al. Peptide–nucleotide microdroplets as a step towards a membrane-free protocell model. Nature Chem 3, 720–724 (2011).

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