Department of Biochemistry, University of Geneva, Geneva, Switzerland.
Department of Theoretical Physics, University of Geneva, Geneva, Switzerland.
Nat Mater. 2022 May;21(5):588-597. doi: 10.1038/s41563-022-01194-5. Epub 2022 Feb 10.
Tissues acquire function and shape via differentiation and morphogenesis. Both processes are driven by coordinating cellular forces and shapes at the tissue scale, but general principles governing this interplay remain to be discovered. Here we report that self-organization of myoblasts around integer topological defects, namely spirals and asters, suffices to establish complex multicellular architectures. In particular, these arrangements can trigger localized cell differentiation or, alternatively, when differentiation is inhibited, they can drive the growth of swirling protrusions. Both localized differentiation and growth of cellular vortices require specific stress patterns. By analysing the experimental velocity and orientational fields through active gel theory, we show that integer topological defects can generate force gradients that concentrate compressive stresses. We reveal these gradients by assessing spatial changes in nuclear volume and deformations of elastic pillars. We propose integer topological defects as mechanical organizing centres controlling differentiation and morphogenesis.
组织通过分化和形态发生获得功能和形状。这两个过程都是由组织尺度上协调的细胞力和形状驱动的,但控制这种相互作用的一般原则仍有待发现。在这里,我们报告说,肌母细胞围绕整数拓扑缺陷(即螺旋和星型)的自组织足以建立复杂的多细胞结构。特别是,这些排列可以触发局部细胞分化,或者,当分化被抑制时,它们可以驱动漩涡状突起的生长。局部分化和细胞涡旋的生长都需要特定的应力模式。通过通过活性凝胶理论分析实验速度和取向场,我们表明整数拓扑缺陷可以产生集中压缩应力的力梯度。我们通过评估核体积的空间变化和弹性支柱的变形来揭示这些梯度。我们提出整数拓扑缺陷作为控制分化和形态发生的机械组织中心。