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Fatty acid membrane assembly on coacervate microdroplets as a step towards a hybrid protocell model

Abstract

Mechanisms of prebiotic compartmentalization are central to providing insights into how protocellular systems emerged on the early Earth. Protocell models are based predominantly on the membrane self-assembly of fatty-acid vesicles, although membrane-free scenarios that involve liquid–liquid microphase separation (coacervation) have also been considered. Here we integrate these alternative models of prebiotic compartmentalization and develop a hybrid protocell model based on the spontaneous self-assembly of a continuous fatty-acid membrane at the surface of preformed coacervate microdroplets prepared from cationic peptides/polyelectrolytes and adenosine triphosphate or oligo/polyribonucleotides. We show that the coacervate-supported membrane is multilamellar, and mediates the selective uptake or exclusion of small and large molecules. The coacervate interior can be disassembled without loss of membrane integrity, and fusion and growth of the hybrid protocells can be induced under conditions of high ionic strength. Our results highlight how notions of membrane-mediated compartmentalization, chemical enrichment and internalized structuration can be integrated in protocell models via simple chemical and physical processes.

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Figure 1: Fatty-acid membrane self-assembly on the surface of positively charged coacervate microdroplets.
Figure 2: DLS and SAXS measurements on coacervate droplets coated with fatty-acid membranes.
Figure 3: Molecular uptake/exclusion from fatty-acid-coated PDDA/ATP and oligolysine/RNA coacervate microdroplets.
Figure 4: Mechanism of coacervate-mediated membrane assembly.
Figure 5: Ionic-strength-induced coacervate disassembly and oleate membrane fusion in hybrid protocells.

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Acknowledgements

We thank the Engineering and Physical Sciences Research Council (EPSRC, UK) and European Research Council (Advanced Grant) for financial support. We thank the EPSRC for a Career Acceleration Fellowship (grant number EP/E038980/1) to M.K.K. and the Malaysian government for the award of a PhD studentship to C.R.C.H. We acknowledge the Wolfson Bioimaging Facility (A. Leard) for assistance with confocal microscopy, beamline I22 (N. Terrill and A. Smith) at Diamond Light Source, W. Briscoe for beamtime and R. Richardson and M. Thomas for assistance and use of software for X-ray analysis. We thank W. Briscoe and J. Eastoe for helpful discussions.

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S.M., A.W.P., T-Y.D.T., M.K.K. and D.S.W. conceived the experiments; C.R.C.H., A.J.T. and T-Y.D.T. performed the experiments; T-Y.D.T., A.J.T. and C.R.C.H. undertook the data analysis; T-Y.D.T., A.J.T., C.R.C.H. and S.M. wrote the manuscript. C.R.C.H. and A.J.T. contributed equally to the work.

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Correspondence to Stephen Mann.

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Dora Tang, TY., Rohaida Che Hak, C., Thompson, A. et al. Fatty acid membrane assembly on coacervate microdroplets as a step towards a hybrid protocell model. Nature Chem 6, 527–533 (2014). https://doi.org/10.1038/nchem.1921

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