The self-assembly of amphiphilic molecules in solution is a ubiquitous process in both natural and synthetic systems. The ability to effectively control the structure and properties of these systems is essential for tuning the quality of their functionality, yet the underlying mechanisms governing the transition from molecules to assemblies have not been fully resolved. Here we describe how amphiphilic self-assembly can be preceded by liquid–liquid phase separation. The assembly of a model block co-polymer system into vesicular structures was probed through a combination of liquid-phase electron microscopy, self-consistent field computations and Gibbs free energy calculations. This analysis shows the formation of polymer-rich liquid droplets that act as a precursor in the bottom-up formation of spherical micelles, which then evolve into vesicles. The liquid–liquid phase separation plays a role in determining the resulting vesicles’ structural properties, such as their size and membrane thickness, and the onset of kinetic traps during self-assembly.
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The matlab script used for image analysis is available from the corresponding author upon reasonable request. The SCF code was provided by F. Leermakers of Wageningen University.
All data supporting the findings of this study, including the SCF input files, the data generated by the SCF computations, and the source data for the figures, are available within the Article and its Supplementary Information and/or from the corresponding authors upon reasonable request
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J.P.P. was supported by the 4TU High-Tech Materials research program ‘New Horizons in Designer Materials’ and the Marie Sklodowska-Curie Action project ‘LPEMM’. H.W. and M.P.V. are supported by the EU H2020 Marie Sklodowska-Curie Action project ‘MULTIMAT’. The authors thank M. Goudzwaard (Eindhoven University of Technology, the Netherlands) for help with making angular maps and radial-averaged intensity maps.
The authors declare no competing interests
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Description of the methodologies used, and supplementary in-depth discussions and supplementary data.
LPEM Movie of the in-situ self-assembly experiment. Unprocessed movie.
LPEM movie of the in-situ self-assembly experiment. Stabilized and cropped movie. Acquisition frame rate: 30 fps; Electron dose rate: 30 electrons.nm-2.s-1; Playback frame rate: 50 fps.
LPEM movie of the membrane formation process of vesicle 1. Electron dose rate: 30 electrons.nm−2.s−1; Playback frame rate: 100 fps.
Control Experiment 1. LPEM movie of pure acetone. Electron dose rate: 30 electrons.nm−2.s−1; Playback frame rate: 80 fps.
Control Experiment 2. LPEM movie of polymer in acetone. Electron dose rate: 30 electrons.nm−2.s−1; Playback frame rate: 80 fps.
Control Experiment 3. Self-assembly of the vesicles in the liquid cell without imaging.
Control Experiment 4. LPEM movie of preformed vesicle.
Control Experiment 6. LPEM movie showing a second example of the in-situ self-assembly experiment.
Control Experiment 6. LPEM movie showing a cropped single particle from Supplementary Movie 8.
Control Experiment 6. LPEM movie shows a third example of the in-situ self-assembly experiment.
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Ianiro, A., Wu, H., van Rijt, M.M.J. et al. Liquid–liquid phase separation during amphiphilic self-assembly. Nat. Chem. 11, 320–328 (2019). https://doi.org/10.1038/s41557-019-0210-4
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