标题： 基于反馈驱动的轴突在平行微图案上延伸的动力学模型 显示英文标题

标题： Feedback-Driven Dynamical Model for Axonal Extension on Parallel Micropatterns

摘要： 尽管在理解神经元发育方面取得了显著进展，但将细胞内机制与轴突生长过程中的环境线索完全整合在一起的定量框架仍不完备。 在这里，我们提出一个统一的生物物理模型，该模型捕捉了控制微图案基底上轴突延伸的关键机械化学过程。 在这些环境中，轴突倾向于沿图案方向排列，形成束状，并以恒定速度前进。 该模型集成了四个核心组件：（i）肌动蛋白-黏附牵引耦合，（ii）相邻轴突之间的侧向抑制，（iii）从胞体到生长锥的微管运输，以及（4）由基质各向异性引导的取向动力学。 动态系统分析表明，肌动蛋白黏附子系统中的鞍结点分岔驱动了向高牵引运动状态的转变，而牵引反馈改变了信号回路中的叉式分岔，促进了对称性破缺和稳健的排列。 微管运输子系统中的精确线性解作为内置的速度调节器，确保了稳定的伸长率。 使用实验推断参数的模拟准确再现了伸长速度、排列方差和束间距。 该模型为通过调节基质硬度和黏附动力学来增强轴突排列提供了明确的设计规则。 通过识别关键控制参数，本工作为神经修复和工程组织系统的生物材料的合理设计奠定了基础。 显示英文摘要

摘要： Despite significant advances in understanding neuronal development, a fully quantitative framework that integrates intracellular mechanisms with environmental cues during axonal growth remains incomplete. Here, we present a unified biophysical model that captures key mechanochemical processes governing axonal extension on micropatterned substrates. In these environments, axons preferentially align with the pattern direction, form bundles, and advance at constant speed. The model integrates four core components: (i) actin-adhesion traction coupling, (ii) lateral inhibition between neighboring axons, (iii) tubulin transport from soma to the growth cone, and (4) orientation dynamics guided by the substrate anisotropy. Dynamical systems analysis reveals that the saddle-node bifurcation in the actin adhesion subsystem drives a transition to a high-traction motile state, while traction feedback shifts a pitchfork bifurcation in the signaling loop, promoting symmetry breaking and robust alignment. An exact linear solution in the tubulin transport subsystem functions as a built-in speed regulator, ensuring stable elongation rates. Simulations using experimentally inferred parameters accurately reproduce elongation speed, alignment variance, and bundle spacing. The model provides explicit design rules for enhancing axonal alignment through modulation of substrate stiffness and adhesion dynamics. By identifying key control parameters, this work enables rational design of biomaterials for neural repair and engineered tissue systems.