Kinetically controlled hetero-fusion is a systems-level behaviour of polymer nanoparticle populations

Stephen D. P. Fielden; Sean M. Collins; Matthew J. Derry; Caterina Ducati; Simon M. Fairclough; Alisha J. Miller; Rachel K. O’Reilly; Paul D. Topham

doi:10.1038/s41467-025-66827-0

Kinetically controlled hetero-fusion is a systems-level behaviour of polymer nanoparticle populations

Stephen D. P. Fielden, Sean M. Collins, Matthew J. Derry, Caterina Ducati, Simon M. Fairclough, Alisha J. Miller, Rachel K. O’Reilly, Paul D. Topham

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Abstract

Particle fusion is key for establishing communication between biological components. For this reason, whole cell fusion plays a crucial role in many processes, including infection, muscle formation and tissue repair. Analogous co-assembly between synthetic nanoparticles represents a similar type of communication mechanism in artificial systems. Other approaches to control such co-assembly rely on incorporating anisotropic recognition units onto particle surfaces to provide a thermodynamic driving force. Here we present a fundamentally different approach, where hetero-fusion between two populations of undecorated polymer nanoparticles is regulated using kinetic control. Fusion extent is tuned simply by adjusting polymer chain length. Fusion is probed using an elemental tagging strategy for cryogenic scanning transmission electron microscopy combined with electron energy loss spectroscopy (cryo-STEM-EELS). Our results demonstrate the emergence of a complex process between populations of synthetic nanoparticles akin to communication. We anticipate such systems-level behaviour that results from hetero-fusion can enable future technologies.

Original language	English
Journal	Nature Communications
Early online date	28 Nov 2025
DOIs	https://doi.org/10.1038/s41467-025-66827-0
Publication status	E-pub ahead of print - 28 Nov 2025

Bibliographical note

Copyright © The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.

Funding

S.D.P.F. is grateful for a Leverhulme Early Career Fellowship (ECF-2021-240, S.D.P.F.) and a Royal Society Dorothy Hodgkin Fellowship (DHF\R1\241133, S.D.P.F.), and to the University of Birmingham for funding. This work was carried out with the support of Diamond Light Source, instrument I22 (proposal SM33098, S.D.P.F., M.J.D., A.J.M., R.K.O.R. and P.D.T.), and we would like to specifically acknowledge the support received by Prof. Nick Terrill, Dr Andy Smith, and Dr Paul Wady during our experiment. The Aston Institute for Membrane Excellence (AIME) is funded by UKRI’s Research England as part of their Expanding Excellence in England (E3) fund. S.M.C. acknowledges support from the EPSRC (EP/X040992/1, S.M.C.). We acknowledge the support of the Wolfson Electron Microscopy Suite and the Thermo Fisher Spectra 300 TEM funded by EPSRC (EP/R008779/1, C.D.). This work was also supported by the Henry Royce Institute for advanced materials through the Equipment Access Scheme, enabling access to the in-situ TEM at Cambridge; Cambridge Royce facilities grant EP/P024947/1 and Sir Henry Royce Institute - recurrent grant EP/R00661X/1.

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10.1038/s41467-025-66827-0Licence: CC BY 4.0

Kinetically controlled hetero-fusion is a systems-level behaviour of polymer nanoparticle populations_ArticleInPress
Copyright © The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.
Accepted author manuscript, 1.34 MBLicence: CC BY 4.0

Cite this

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Kinetically controlled hetero-fusion is a systems-level behaviour of polymer nanoparticle populations

Abstract

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