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Published February 2024 | Published
Journal Article Open

Magneto-acoustic protein nanostructures for non-invasive imaging of tissue mechanics in vivo

Abstract

Measuring cellular and tissue mechanics inside intact living organisms is essential for interrogating the roles of force in physiological and disease processes. Current agents for studying the mechanobiology of intact, living organisms are limited by poor light penetration and material stability. Magnetomotive ultrasound is an emerging modality for real-time in vivo imaging of tissue mechanics. Nonetheless, it has poor sensitivity and spatiotemporal resolution. Here we describe magneto-gas vesicles (MGVs), protein nanostructures based on gas vesicles and magnetic nanoparticles that produce differential ultrasound signals in response to varying mechanical properties of surrounding tissues. These hybrid nanomaterials significantly improve signal strength and detection sensitivity. Furthermore, MGVs enable non-invasive, long-term and quantitative measurements of mechanical properties within three-dimensional tissues and in vivo fibrosis models. Using MGVs as novel contrast agents, we demonstrate their potential for non-invasive imaging of tissue elasticity, offering insights into mechanobiology and its application to disease diagnosis and treatment.

Copyright and License

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

Acknowledgement

This work was supported by the Institute for Basic Science (IBS-R026-D1, to J.-H.L, M.K., S.-W.C. and J.C.). This work was also supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government, the Ministry of Science and ICT (MSIT) (numbers 2021R1A2C3004262 and 2022M3A9B6082675) and Samsung Research Funding & Incubation Center of Samsung Electronics under project number SRFC-TC2003-03 to S.-W.C. This research was also supported by the Yonsei Signature Research Cluster Program of 2023-22-0012 and the Yonsei Fellow Program funded by Lee Youn Jae to S.-W.C. This work was also supported by the US National Institutes of Health (R01-EB018975) to M.G.S. E.C.-H. was supported by the James G. Boswell Fellowship in Molecular Engineering and MRI. M.G.S. is an Investigator of the Howard Hughes Medical Institute (HHMI).

This article is subject to HHMI's Open Access to Publications policy. HHMI Investigators have previously granted a non-exclusive CC BY 4.0 license to the public and a sublicensable license to HHMI in their research articles. Pursuant to those licenses, the author-accepted manuscript of this article can be made freely available under a CC BY 4.0 license immediately upon publication.

Contributions

These authors contributed equally: Whee-Soo Kim, Sungjin Min.

W.-S.K. performed overall in vitro and in vivo experiments and analysed data. S.M designed and performed organoid-related experiments. S.K.K., Y.H.K. and S.A. supported hiPSC differentiation, MMUS imaging and hydrogel characterization, respectively. S.K. provided magnetic nanoparticles. E.C.-H. supported the measurements of ultrasound signals using hydrophones. H.D. and A.B.-Z. performed initial set-up and discussions on this research. D.M. provided gas vesicles. J.-H.L. helped with initial set-up and discussions on this research. S.H.B. and J.G.L. provided lung tissue for the organoid development. M.K. assisted with the design of research and experiment. W.-S.K and M.K. wrote the manuscript with input from all authors. S.-W.C., M.G.S. and J.C. conceived and supervised the project.

Data Availability

The data presented in this study are available in the Source data. Additional information and requests for resources and reagents that support the findings of this study are available from the corresponding author upon reasonable request. Source data are provided with this paper.

Code Availability

Ultrasound data acquisition and analysis code is available on the Shapiro laboratory GitHub at https://github.com/shapiro-lab.

Conflict of Interest

The authors declare no competing interests.

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Additional details

Created:
February 21, 2024
Modified:
February 21, 2024