Sequential Release of Proteins from Structured Multishell Microcapsules

Ulyana Shimanovich, Thomas C.T. Michaels, Erwin De Genst, Dijana Matak-Vinkovic, Christopher M. Dobson, Tuomas P.J. Knowles

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


In nature, a wide range of functional materials is based on proteins. Increasing attention is also turning to the use of proteins as artificial biomaterials in the form of films, gels, particles, and fibrils that offer great potential for applications in areas ranging from molecular medicine to materials science. To date, however, most such applications have been limited to single component materials despite the fact that their natural analogues are composed of multiple types of proteins with a variety of functionalities that are coassembled in a highly organized manner on the micrometer scale, a process that is currently challenging to achieve in the laboratory. Here, we demonstrate the fabrication of multicomponent protein microcapsules where the different components are positioned in a controlled manner. We use molecular self-assembly to generate multicomponent structures on the nanometer scale and droplet microfluidics to bring together the different components on the micrometer scale. Using this approach, we synthesize a wide range of multiprotein microcapsules containing three well-characterized proteins: glucagon, insulin, and lysozyme. The localization of each protein component in multishell microcapsules has been detected by labeling protein molecules with different fluorophores, and the final three-dimensional microcapsule structure has been resolved by using confocal microscopy together with image analysis techniques. In addition, we show that these structures can be used to tailor the release of such functional proteins in a sequential manner. Moreover, our observations demonstrate that the protein release mechanism from multishell capsules is driven by the kinetic control of mass transport of the cargo and by the dissolution of the shells. The ability to generate artificial materials that incorporate a variety of different proteins with distinct functionalities increases the breadth of the potential applications of artificial protein-based materials and provides opportunities to design more refined functional protein delivery systems.

Original languageEnglish
Pages (from-to)3052-3059
Number of pages8
Issue number10
StatePublished - 9 Oct 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 American Chemical Society.


We thank Elan Pharmaceuticals (U.S., C.M.D., T.P.J.K.), the BBSRC (T.P.J.K.), the Frances and Augustus Newman Foundation, Welcome Trust (T.P.J.K., C.M.D.), Swiss National Science Foundation (T.C.T.M.), and Peterhouse College, Cambridge (T.C.T.M.). The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) through the ERC grant PhysProt (agreement no. 337969). U.S. thanks Peter and Patricia Gruber, the Benoziyo Fund for the Advancement of Science, the Yad Hanadiv foundation and the Lustgarten Georges Foundation.

FundersFunder number
Benoziyo Fund for the Advancement of Science
Yad Hanadiv Foundation
Lustgarten Foundation
European Research Council337969
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung164931
Seventh Framework Programme


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