Self-assembly of structured colloidal gels for high resolution 3d micropatterning of proteins at scale
Self-assembly of structured colloidal gels for high resolution 3d micropatterning of proteins at scale
Self-assembly, the spontaneous ordering of components into patterns, is widespread in nature and fundamental to generating function across length scales. Morphogen gradients in biological development are paradigmatic as both products and effectors of self-assembly and various attempts have been made to reproduce such gradients in biomaterial design. To date, approaches have typically utilized top-down fabrication techniques that, while allowing high-resolution control, are limited by scale and require chemical cross-linking steps to stabilize morphogen patterns in time. Here, a bottom-up approach to protein patterning is developed based on a novel binary reaction-diffusion process where proteins function as diffusive reactants to assemble a nanoclay-protein composite hydrogel. Using this approach, it is possible to generate scalable and highly stable 3D patterns of target proteins down to sub-cellular resolution through only physical interactions between clay nanoparticles and the proteins and ions present in blood. Patterned nanoclay gels are able to guide cell behavior to precisely template bone tissue formation in vivo. These results demonstrate the feasibility of stabilizing 3D gradients of biological signals through self-assembly processes and open up new possibilities for morphogen-based therapeutic strategies and models of biological development and repair.
3D micropatterning, diffusion-reaction, nanoparticles, protein delivery, self-organization
Ramnarine-Sanchez, Roxanna Sharon
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Kanczler, Janos M.
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Evans, Nicholas D.
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Oreffo, Richard O.C.
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Dawson, Jonathan I.
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28 November 2023
Ramnarine-Sanchez, Roxanna Sharon
9be7d4c2-c668-4e89-a8ef-238c6796a1be
Kanczler, Janos M.
eb8db9ff-a038-475f-9030-48eef2b0559c
Evans, Nicholas D.
06a05c97-bfed-4abb-9244-34ec9f4b4b95
Oreffo, Richard O.C.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Dawson, Jonathan I.
982bf202-af02-4a6c-9db0-2d4a72c1ea92
Ramnarine-Sanchez, Roxanna Sharon, Kanczler, Janos M., Evans, Nicholas D., Oreffo, Richard O.C. and Dawson, Jonathan I.
(2023)
Self-assembly of structured colloidal gels for high resolution 3d micropatterning of proteins at scale.
Advanced Materials, 35 (48), [2304461].
(doi:10.1002/adma.202304461).
Abstract
Self-assembly, the spontaneous ordering of components into patterns, is widespread in nature and fundamental to generating function across length scales. Morphogen gradients in biological development are paradigmatic as both products and effectors of self-assembly and various attempts have been made to reproduce such gradients in biomaterial design. To date, approaches have typically utilized top-down fabrication techniques that, while allowing high-resolution control, are limited by scale and require chemical cross-linking steps to stabilize morphogen patterns in time. Here, a bottom-up approach to protein patterning is developed based on a novel binary reaction-diffusion process where proteins function as diffusive reactants to assemble a nanoclay-protein composite hydrogel. Using this approach, it is possible to generate scalable and highly stable 3D patterns of target proteins down to sub-cellular resolution through only physical interactions between clay nanoparticles and the proteins and ions present in blood. Patterned nanoclay gels are able to guide cell behavior to precisely template bone tissue formation in vivo. These results demonstrate the feasibility of stabilizing 3D gradients of biological signals through self-assembly processes and open up new possibilities for morphogen-based therapeutic strategies and models of biological development and repair.
Text
Advanced Materials - 2023 - Ramnarine‐Sanchez - Self‐assembly of Structured Colloidal Gels for High Resolution 3d
- Accepted Manuscript
More information
e-pub ahead of print date: 2 September 2023
Published date: 28 November 2023
Additional Information:
Funding Information:
The authors are grateful to the Engineering and Physical Sciences Research Council (EPSRC, EP/L010259/1 and EP/S017054/1) and the University of Southampton for funding the project. The authors thank members of the Biomedical Imaging Unit of the University of Southampton for their help with sample processing, different imaging techniques used in this paper, and 3D printing, particularly D. Johnstone, R. Doherty, K. Dexter, G. Patricia, and A. Page. The authors would also like to thank A. Janeczek and P. Duriez for advice with protein labeling and purification, J. Wells for histology sample processing, and J. Van Duijneveldt for contribution to the diffusion profile analysis.
Publisher Copyright:
© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.
Keywords:
3D micropatterning, diffusion-reaction, nanoparticles, protein delivery, self-organization
Identifiers
Local EPrints ID: 482476
URI: http://eprints.soton.ac.uk/id/eprint/482476
ISSN: 1521-4095
PURE UUID: a8de8955-e903-4085-b64b-871cc468e356
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Date deposited: 09 Oct 2023 16:38
Last modified: 18 Mar 2024 03:16
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Contributors
Author:
Roxanna Sharon Ramnarine-Sanchez
Author:
Janos M. Kanczler
Author:
Jonathan I. Dawson
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