Cellular self-organization by autocatalytic alignment feedback
Cellular self-organization by autocatalytic alignment feedback
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DOI：
10.1242/jcs.088898
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发表时间：
2011-12-15
影响因子：
4
通讯作者：
Wong, Pak Kin
中科院分区：
文献类型：
--
作者：
Junkin, Michael;Leung, Siu Ling;Wong, Pak Kin
成肌细胞在胚胎发生和组织再生过程中聚集、分化和融合形成骨骼肌。对于适当的肌肉功能，需要成肌细胞的远程自组织来创建与邻近组织整体对齐的有组织的肌肉结构。然而，细胞如何在比单个细胞长得多的距离上处理几何信息，从而自组织成有序、排列整齐的多核肌纤维，仍然是发育生物学和再生医学的中心问题。使用等离子体光刻微图案化来创建用于细胞引导的空间线索，我们展示了一种物理机制，通过该机制，方位信息可以从几何边界传播到远距离，以指导肌肉组织的发育。这种长程排列只发生在分化的成肌细胞中，但不存在于受到微流体干扰或其他非融合细胞类型干扰的非融合成肌细胞中。计算细胞自动机对自组织过程的时空演化的分析表明，肌源性融合与旋转惯性功能以一种自强化的方式相结合，以增强对齐信息的远程传播。有了这种自动催化的排列反馈，肌肉的有序排列可以加强现有的方向，并有助于促进与邻近组织和整体组织的正确排列。这种物理上的自我增强可能是组织形态发生过程中长程图案形成的基本机制。
Myoblasts aggregate, differentiate and fuse to form skeletal muscle during both embryogenesis and tissue regeneration. For proper muscle function, long-range self-organization of myoblasts is required to create organized muscle architecture globally aligned to neighboring tissue. However, how the cells process geometric information over distances considerably longer than individual cells to self-organize into well-ordered, aligned and multinucleated myofibers remains a central question in developmental biology and regenerative medicine. Using plasma lithography micropatterning to create spatial cues for cell guidance, we show a physical mechanism by which orientation information can propagate for a long distance from a geometric boundary to guide development of muscle tissue. This long-range alignment occurs only in differentiating myoblasts, but not in non-fusing myoblasts perturbed by microfluidic disturbances or other non-fusing cell types. Computational cellular automata analysis of the spatiotemporal evolution of the self-organization process reveals that myogenic fusion in conjunction with rotational inertia functions in a self-reinforcing manner to enhance long-range propagation of alignment information. With this autocatalytic alignment feedback, well-ordered alignment of muscle could reinforce existing orientations and help promote proper arrangement with neighboring tissue and overall organization. Such physical self-enhancement might represent a fundamental mechanism for long-range pattern formation during tissue morphogenesis.