DNA nanomachines reveal an adaptive energy mode in confinement-induced amoeboid migration powered by polarized mitochondrial distribution

Energy metabolism is highly interdependent with adaptive cell migration in vivo. Mechanical confinement is a critical physical cue that induces switchable migration modes of the mesenchymal-to-amoeboid transition (MAT). However, the energy states in distinct migration modes, especially amoeboid-like...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 121; no. 14; p. e2317492121
Main Authors Liu, Yixin, Wang, Ya-Jun, Du, Yang, Liu, Wei, Huang, Xuedong, Fan, Zihui, Lu, Jiayin, Yi, Runqiu, Xiang, Xiao-Wei, Xia, Xinwei, Gu, Hongzhou, Liu, Yan-Jun, Liu, Baohong
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 02.04.2024
Subjects
Amoeba
ATP
Biological Sciences
Biomimetics
Cell Line, Tumor
Cell migration
Cell Movement
Confinement
Cytoskeleton
Deoxyribonucleic acid
DNA
Energy
Energy conservation
Energy distribution
Energy metabolism
Metabolism
Metabolomics
Metastases
Microenvironments
Mitochondria
Modes
Particle tracking
Physical Phenomena
Therapeutic applications
DNA nanomachines
distinct migration modes
mechanical confinement
an energy-saving mode
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Summary:Energy metabolism is highly interdependent with adaptive cell migration in vivo. Mechanical confinement is a critical physical cue that induces switchable migration modes of the mesenchymal-to-amoeboid transition (MAT). However, the energy states in distinct migration modes, especially amoeboid-like stable bleb (A2) movement, remain unclear. In this report, we developed multivalent DNA framework-based nanomachines to explore strategical mitochondrial trafficking and differential ATP levels during cell migration in mechanically heterogeneous microenvironments. Through single-particle tracking and metabolomic analysis, we revealed that fast A2-moving cells driven by biomimetic confinement recruited back-end positioning of mitochondria for powering highly polarized cytoskeletal networks, preferentially adopting an energy-saving mode compared with a mesenchymal mode of cell migration. We present a versatile DNA nanotool for cellular energy exploration and highlight that adaptive energy strategies coordinately support switchable migration modes for facilitating efficient metastatic escape, offering a unique perspective for therapeutic interventions in cancer metastasis.
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Edited by David Weitz, Harvard University, Cambridge, MA; received October 10, 2023; accepted February 19, 2024
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.2317492121