He Jun-Xi, Sui Bing-Dong, Jin Yan, Zheng Chen-Xi, Jin Fang
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Cell Biosci. 2025 Jul 13;15(1):101. doi: 10.1186/s13578-025-01429-3.
The emergence of complex tissue architectures from homogeneous stem cell condensates persists as a central enigma in developmental biology. While biochemical signaling gradients have long dominated explanations of organ patterning, the mechanistic interplay between tissue-scale forces and thermodynamic constraints in driving symmetry breaking remains unresolved. This review unveils supracellular actin networks as mechanochemical integrators that establish developmental tensegrity structures, wherein Brownian ratchet-driven polymerization generates patterned stress fields to guide condensate stratification. Central to this paradigm is the dynamic remodeling of actin branches, which transduce mechanical loads into adaptive network architectures through force-modulated capping kinetics and angular reorientation. Such plasticity enables fluid-to-solid phase transitions, stabilizing organ primordia through viscoelastic microdomain formation. Crucially, these biophysical processes are functionally coupled with metabolic reprogramming events, where cytoskeletal strain modulates glycolytic flux and nuclear mechanotransduction pathways to inform differentiation decisions, forging a feedback loop between tissue mechanics and cellular fate specification. Building on these insights, we argue that limitations in current organoid self-organization may originate from incomplete reconstitution of actin-mediated mechanical coherence, and modeling of heterogeneous mesenchymal condensation dynamics offers a strategic framework to decode self-organization trajectories, bridging developmental principles with regenerative design. By synthesizing advances from molecular biophysics to tissue mechanics, this work reframes organogenesis not as a hierarchy of molecular commands, but as an emergent continuum where biochemical, mechanical, and thermodynamic constraints coevolve to sculpt living architectures.
从均匀的干细胞凝聚物中形成复杂的组织结构，一直是发育生物学中的核心谜题。虽然生化信号梯度长期以来主导着器官模式形成的解释，但组织尺度力与热力学约束在驱动对称性破缺过程中的机制相互作用仍未得到解决。这篇综述揭示了细胞外肌动蛋白网络作为机械化学整合器，建立发育中的张拉整体结构，其中布朗棘轮驱动的聚合作用产生有图案的应力场来引导凝聚物分层。这一范式的核心是肌动蛋白分支的动态重塑，它通过力调制的封端动力学和角度重新定向将机械负荷转化为适应性网络结构。这种可塑性使得流体到固体的相变成为可能，通过粘弹性微区的形成来稳定器官原基。至关重要的是，这些生物物理过程在功能上与代谢重编程事件相耦合，其中细胞骨架应变调节糖酵解通量和核机械转导途径以指导分化决策，在组织力学和细胞命运特化之间形成一个反馈回路。基于这些见解，我们认为当前类器官自组织的局限性可能源于肌动蛋白介导的机械连贯性的不完全重构，而异质间充质凝聚动力学的建模提供了一个战略框架来解码自组织轨迹，将发育原理与再生设计联系起来。通过综合从分子生物物理学到组织力学的进展，这项工作将器官发生重新定义为不是分子指令的层级，而是一个生化、机械和热力学约束共同进化以塑造生命结构的涌现连续体。
