Li Changhao, Nijjer Japinder, Feng Luyi, Zhang Qiuting, Yan Jing, Zhang Sulin
Department of Engineering Science and Mechanics, Pennsylvania State University, University Park, PA, USA.
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA.
Soft Matter. 2024 Apr 24;20(16):3401-3410. doi: 10.1039/d3sm01535a.
Living active collectives have evolved with remarkable self-patterning capabilities to adapt to the physical and biological constraints crucial for their growth and survival. However, the intricate process by which complex multicellular patterns emerge from a single founder cell remains elusive. In this study, we utilize an agent-based model, validated through single-cell microscopy imaging, to track the three-dimensional (3D) morphodynamics of cells within growing bacterial biofilms encased by agarose gels. The confined growth conditions give rise to a spatiotemporally heterogeneous stress landscape within the biofilm. In the core of the biofilm, where high hydrostatic and low shear stresses prevail, cell packing appears disordered. In contrast, near the gel-cell interface, a state of high shear stress and low hydrostatic stress emerges, driving nematic ordering, albeit with a time delay inherent to shear stress relaxation. Strikingly, we observe a robust spatiotemporal correlation between stress anisotropy and nematic ordering within these confined biofilms. This correlation suggests a mechanism whereby stress anisotropy plays a pivotal role in governing the spatial organization of cells. The reciprocity between stress anisotropy and cell ordering in confined biofilms opens new avenues for innovative 3D mechanically guided patterning techniques for living active collectives, which hold significant promise for a wide array of environmental and biomedical applications.
活跃的生物聚集体不断进化，具备显著的自我模式形成能力，以适应对其生长和生存至关重要的物理和生物限制因素。然而，从单个起始细胞形成复杂多细胞模式的复杂过程仍然难以捉摸。在本研究中，我们利用基于代理的模型，通过单细胞显微镜成像进行验证，以追踪琼脂糖凝胶包裹的生长细菌生物膜内细胞的三维（3D）形态动力学。受限的生长条件在生物膜内产生了时空异质的应力格局。在生物膜的核心区域，高静水压力和低剪切应力占主导，细胞堆积显得无序。相比之下，在凝胶 - 细胞界面附近，出现了高剪切应力和低静水压力的状态，驱动向列相有序排列，尽管剪切应力松弛存在固有的时间延迟。引人注目的是，我们在这些受限生物膜中观察到应力各向异性与向列相有序排列之间存在强大的时空相关性。这种相关性表明了一种机制，即应力各向异性在控制细胞的空间组织中起着关键作用。受限生物膜中应力各向异性与细胞排列之间的相互作用为活跃生物聚集体的创新3D机械引导图案化技术开辟了新途径，这在广泛的环境和生物医学应用中具有巨大潜力。
