近日，美国布朗大学Wong, Ian Y.团队研究了三维多细胞球体从轨道到基质侵袭的集体转变。2026年1月26日，《自然—物理学》杂志发表了这一成果。

上皮细胞通过沿弯曲基质界面的协同旋转，能够将上皮组织塑造成球形形态。随后，通过限制性基质的局部重塑，可能发生多细胞链或分支的径向侵袭。这些对称性破缺转变源于细胞与基质间的动态互馈，但其机制尚不明确。

研究组显示，上皮细胞球体通过与周围基质曲率的双向相互作用，集体从环绕运动转变为径向侵袭。起初，球体呈椭球状，但随环绕运动逐渐变圆。反过来，沿更尖锐曲率运动时会产生局部更强的收缩牵引力，逐渐使胶原纤维沿径向排列。因此，初始的伸长形态促使基质后续被二至四条大致沿其长轴排列的细胞链侵袭。

研究还发现，利用渗透压可阻止环绕运动并逆转侵袭过程。在嵌合球体中探究协同环绕运动时发现，即使少量细胞间黏附减弱的细胞也能阻碍集体环绕，但仍能侵袭基质。这项工作阐明了组织形态发生中的对称性破缺如何受集体迁移与细胞-基质界面局部曲率相互作用的调控，对胚胎发育和肿瘤进展研究具有重要启示。

附：英文原文

Title: Collective transitions from orbiting to matrix invasion in three-dimensional multicellular spheroids

Author: Kim, Jiwon, Jeong, Hyuntae, Falc, Carles, Hruska, Alex M., Martinson, W. Duncan, Marzoratti, Alejandro, Araiza, Mauricio, Yang, Haiqian, Fonseca, Vera C., Adam, Stephen A., Franck, Christian, Carrillo, Jos A., Guo, Ming, Wong, Ian Y.

Issue&Volume: 2026-01-26

Abstract: Coordinated cell rotation along a curved matrix interface can sculpt epithelial tissues into spherical morphologies. Subsequently, radially oriented invasion of multicellular strands or branches can occur by local remodelling of the confining matrix. These symmetry-breaking transitions emerge from the dynamic reciprocity between cells and matrix but remain poorly understood. Here we show that epithelial cell spheroids collectively transition from circumferential orbiting to radial invasion via bidirectional interactions with the surrounding matrix curvature. Initially, spheroids exhibit an ellipsoidal shape but become rounded as orbiting occurs. In turn, orbiting along sharper curvature results in locally stronger contractile tractions, which gradually align collagen fibres in the radial direction. Thus, the initially elongated morphology primes the matrix towards subsequent invasion of two to four strands that are roughly aligned with its major axis. We then show that orbiting can be arrested and invasion can be reversed using osmotic pressure. We also investigate coordinated orbiting in mosaic spheroids, showing that a small fraction of cells with weakened cell–cell adhesions can impede collective orbiting but still invade into the matrix. This work elucidates how symmetry breaking in tissue morphogenesis is governed by the interplay of collective migration and the local curvature of the cell–matrix interface, with relevance for embryonic development and tumour progression.

DOI: 10.1038/s41567-025-03150-x

Source: https://www.nature.com/articles/s41567-025-03150-x