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

• 成果类型: Article
• 署名作者: 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
• 署名单位: Fudan University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10042
• DOI: 10.1073/pnas.2317492121
• 发表日期: 2024-04-02
• 关键词: cell-migration; TRAFFICKING; plasticity; metabolism; DYNAMICS; shapes; single

摘要

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.