Feedback-controlled dynamics of neuronal cells on directional surfaces
Feedback-controlled dynamics of neuronal cells on directional surfaces
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DOI：
10.1016/j.bpj.2022.01.020
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发表时间：
2022-03-01
影响因子：
3.4
通讯作者：
Staii, Cristian
中科院分区：
文献类型：
--
作者：
Descoteaux, Marc;Sunnerberg, Jacob P.;Staii, Cristian
神经元网络的形成是一个复杂的现象，对于理解神经系统的发育具有根本的重要性。网络形成的基本过程是轴突生长，该过程涉及轴突从细胞体延伸以及轴突向目标神经元导航。轴突生长是由轴突尖端（生长锥）与其细胞外环境线索之间的相互作用引导的，这些相互作用包括细胞间相互作用、神经元周围的生化景观以及生长基质的机械和几何特征。在这里，我们提出了一个全面的实验和理论分析的轴突生长的神经元微图案化聚二甲基硅氧烷（PDMS）表面上培养。我们证明，闭环反馈是这些表面上的轴突动力学的一个重要组成部分：生长锥不断测量环境线索，并调整其运动响应外部几何特征。我们发现，这个模型捕捉到的所有特性的轴突动力学的PDMS表面的未经处理的和化学修饰的神经元。我们将联合收割机的实验数据与理论分析相结合，测量描述轴突动力学的关键参数：扩散（细胞运动）系数，速度和角度分布，以及细胞-基质相互作用。在用Taxol（微管动力学抑制剂）和Y-27632（肌动蛋白丝破坏剂）处理的神经元上进行的实验表明，微管和肌动蛋白丝的内部动力学对于反馈机制的适当功能起着关键作用。我们的研究结果表明，轴突通过接触引导机制，其中高曲率的几何特征赋予高牵引力的生长锥的几何图案。这些结果对于我们理解轴突生长以及寻找新的生物工程基质来引导神经元生长和促进神经修复具有重要意义。
The formation of neuronal networks is a complex phenomenon of fundamental importance for understanding the development of the nervous system. The basic process underlying the network formation is axonal growth, a process involving the extension of axons from the cell body and axonal navigation toward target neurons. Axonal growth is guided by the interactions between the tip of the axon (growth cone) and its extracellular environmental cues, which include intercellular interactions, the biochemical landscape around the neuron, and the mechanical and geometrical features of the growth substrate. Here, we present a comprehensive experimental and theoretical analysis of axonal growth for neurons cultured on micropatterned polydimethylsiloxane (PDMS) surfaces. We demonstrate that closed-loop feedback is an essential component of axonal dynamics on these surfaces: the growth cone continuously measures environmental cues and adjusts its motion in response to external geometrical features. We show that this model captures all the characteristics of axonal dynamics on PDMS surfaces for both untreated and chemically modified neurons. We combine experimental data with theoretical analysis to measure key parameters that describe axonal dynamics: diffusion (cell motility) coefficients, speed and angular distributions, and cell-substrate interactions. The experiments performed on neurons treated with Taxol (inhibitor of microtubule dynamics) and Y-27632 (disruptor of actin filaments) indicate that the internal dynamics of microtubules and actin filaments plays a critical role for the proper function of the feedback mechanism. Our results demonstrate that axons follow geometrical patterns through a contact-guidance mechanism, in which high-curvature geometrical features impart high traction forces to the growth cone. These results have important implications for our fundamental understanding of axonal growth as well as for bioengineering novel substrate to guide neuronal growth and promote nerve repair.