Anomalous and heterogeneous DNA transport in biomimetic cytoskeleton networks
Anomalous and heterogeneous DNA transport in biomimetic cytoskeleton networks
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DOI：
10.1039/d0sm00544d
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发表时间：
2020-07-21
期刊：
影响因子：
3.4
通讯作者：
Robertson-Anderson, Rae M.
中科院分区：
文献类型：
--
作者：
Garamella, Jonathan;Regan, Kathryn;Robertson-Anderson, Rae M.
细胞骨架是蛋白质丝和交联蛋白质的复杂网络，决定着从分裂到货物运输的多种细胞过程。然而，细胞骨架在 DNA 和其他大分子的细胞内运输中所起的作用仍然知之甚少。在这里，我们使用单分子构象追踪，测量了具有不同交联类型的肌动蛋白和微管复合网络中线性和松弛环状（环）DNA 的运输和构象动力学。虽然线性和环状 DNA 都会经历异常、非高斯和非遍历的次扩散，但详细的动力学是由 DNA 拓扑（线性与环状）和交联基序控制的。环状 DNA 膨胀，表现出通过细胞骨架丝的螺纹控制的异质亚扩散，而线性 DNA 压缩，表现出通过笼养和跳跃进行运输。重要的是，虽然交联基序对环状 DNA 几乎没有影响，但与肌动蛋白-肌动蛋白或微管-微管交联相比，肌动蛋白-微管交联网络中的线性 DNA 遍历性明显较低，并且显示出更多的异质运输。
The cytoskeleton, a complex network of protein filaments and crosslinking proteins, dictates diverse cellular processes ranging from division to cargo transport. Yet, the role the cytoskeleton plays in the intracellular transport of DNA and other macromolecules remains poorly understood. Here, using single-molecule conformational tracking, we measure the transport and conformational dynamics of linear and relaxed circular (ring) DNA in composite networks of actin and microtubules with variable types of crosslinking. While both linear and ring DNA undergo anomalous, non-Gaussian, and non-ergodic subdiffusion, the detailed dynamics are controlled by both DNA topology (linearvs.ring) and crosslinking motif. Ring DNA swells, exhibiting heterogeneous subdiffusion controlledviathreading by cytoskeleton filaments, while linear DNA compacts, exhibiting transportviacaging and hopping. Importantly, while the crosslinking motif has little effect on ring DNA, linear DNA in networks with actin-microtubule crosslinking is significantly less ergodic and shows more heterogeneous transport than with actin-actin or microtubule-microtubule crosslinking.