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Stimuli-responsive polypeptide vesicles by conformation-specific assembly

Abstract

In biology, lipids are well known for their ability to assemble into spherical vesicles1. Proteins, in particular virus capsids, can also form regular vesicle-like structures, where the precise folding and stable conformations of many identical subunits directs their self-assembly2. Functionality present on these subunits also controls their disassembly within the cellular environment, for example, in response to a pH change3. Here, we report the preparation of diblock copolypeptides that self-assemble into spherical vesicular assemblies whose size and structure are dictated primarily by the ordered conformations of the polymer segments, in a manner similar to viral capsid assembly. Furthermore, functionality was incorporated into these molecules to render them susceptible to environmental stimuli, which is desirable for drug-delivery applications. The control of assembly and function exhibited in these systems is a significant advance towards the synthesis of materials that can mimic the precise three-dimensional assembly found in proteins.

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Figure 1: Images of different KPxLy samples for 1.0-wt% copolymer suspensions in deionized water.
Figure 2: KP100L20 samples of different stereochemistry.
Figure 3: pH-responsive vesicles.

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Acknowledgements

The authors thank Kelly D. Hales (University of Delaware) for assistance with the DLS measurements. This work was supported by grants from the National Science Foundation (Award No. CTS-9986347 and CTS-0103516), the Arnold and Mabel Beckman Foundation, and partially supported by the MRSEC program of the National Science Foundation under award No. DMR-0080034. This work used SANS facilities supported in part by the National Science Foundation under Agreement No. DMR-9986442, the National Institute of Standards and Technology, and the US Department of Commerce.

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Correspondence to Timothy J. Deming.

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Bellomo, E., Wyrsta, M., Pakstis, L. et al. Stimuli-responsive polypeptide vesicles by conformation-specific assembly. Nature Mater 3, 244–248 (2004). https://doi.org/10.1038/nmat1093

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