PDF(Pubmed)
Abstract：
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.
摘要：
能量代谢与体内适应性细胞迁移高度相互依存。机械限制是诱导间充质到变形虫转变（MAT）的可切换迁移模式的关键物理线索。然而,处于不同迁移模式的能量状态，尤其是变形虫状的稳定气泡(A2)运动，仍然不清楚。在这份报告中,我们开发了基于多价DNA框架的纳米机器，以探索机械异质微环境中细胞迁移过程中的战略性线粒体运输和差异ATP水平。通过单粒子跟踪和代谢组学分析，我们发现，由仿生限制驱动的快速A2移动细胞招募了线粒体的后端定位，为高度极化的细胞骨架网络提供动力，与细胞迁移的间充质模式相比，优先采用节能模式。我们提出了一种用于细胞能量探索的多功能DNA纳米工具，并强调自适应能量策略协调支持可切换的迁移模式，以促进有效的转移逃逸。为癌症转移的治疗干预提供了独特的视角。
