近日，清华大学生物力学与医学工程研究所的李博及其研究团队取得一项新进展。经过不懈努力，他们揭示上皮样组织中活跃的孔洞形成过程。相关研究成果已于2024年5月15日在国际知名学术期刊《自然—物理学》上发表。
本研究表明，在人胚胎干细胞衍生的上皮样单层组织中，活跃的细胞收缩可以自发地启动由孔成核、聚并和网络形成组成的形态转变级联。累积的组织水平拉应力推动孔洞从均匀的圆形逐渐扩展，直至在细胞间连接处发生局部断裂。随后，裂纹迅速扩展，但随后被细胞自组织的肌动球蛋白环所抑制，并伴随着裂纹的钝化及断裂向圆角的转变。
在孔洞合并过程中，研究团队揭示了一种断裂-滑移机制，该机制能够实现多细胞桥的逐层断裂，同时避免过度的细胞变形。这一多尺度理论不仅准确捕捉了这些实验现象，还预测了细胞基质刚性感知和细胞粘附与细胞收缩之间的竞争，从而影响了形态动力学。这些发现表明，活体组织能在分子、细胞和组织层面协调力学作用，以驱动拓扑变化，同时降低细胞机械损伤的风险。
据悉，上皮组织中孔洞的形成对发育至关重要，但它也可能与上皮屏障功能障碍和癌症进展有关。
附：英文原文
Title: Active hole formation in epithelioid tissues
Author: Lv, Jian-Qing, Chen, Peng-Cheng, Chen, Yun-Ping, Liu, Hao-Yu, Wang, Shi-Da, Bai, Jianbo, Lv, Cheng-Lin, Li, Yue, Shao, Yue, Feng, Xi-Qiao, Li, Bo
Issue&Volume: 2024-05-15
Abstract: The formation of holes in epithelial tissue is essential for development, but it can also be associated with epithelial barrier dysfunction and cancer progression. Here we show that active cell contraction in epithelioid monolayer tissues derived from human embryonic stem cells can spontaneously launch a morphological transition cascade consisting of hole nucleation, coalescence and network formation. Accumulated tissue-level tensile stresses drive hole expansion from isotropic round expansion to local fracture of intercellular junctions. This is followed by fast crack propagation, which is later suppressed by the self-organized supracellular actomyosin ring and accompanied by crack blunting and a fracture-to-rounding transition. During hole coalescence, we find a fracture–slip mechanism that enables layer-by-layer breaking of the multicellular bridge but without inducing excessive cell deformation. Our multiscale theory captures these experimental observations and predicts that substrate rigidity sensing and adhesion of cells compete with cellular contraction to mediate the morphological dynamics. These findings suggest that living tissues may coordinate the mechanics across molecular, cellular and tissue scales to drive topological changes while reducing the risk of mechanical damage to cells.
DOI: 10.1038/s41567-024-02504-1
Source: https://www.nature.com/articles/s41567-024-02504-1