Schoenit Andreas, Monfared Siavash, Anger Lucas, Rosse Carine, Venkatesh Varun, Balasubramaniam Lakshmi, Marangoni Elisabetta, Chavrier Philippe, Mège René-Marc, Doostmohammadi Amin, Ladoux Benoit
Université Paris Cité, CNRS, Institut Jacques Monod, Paris, France.
Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.
Nat Mater. 2025 Mar 14. doi: 10.1038/s41563-025-02150-9.
Cell competition is a tissue surveillance mechanism for eliminating unwanted cells, being indispensable in development, infection and tumourigenesis. Although studies have established the role of biochemical mechanisms in this process, due to challenges in measuring forces in these systems, how mechanical forces determine the competition outcome remains unclear. Here we report a form of cell competition that is regulated by differences in force transmission capabilities, selecting for cell types with stronger intercellular adhesion. Direct force measurements in ex vivo tissues and different cell lines reveal that there is an increased mechanical activity at the interface between two competing cell types, which can lead to large stress fluctuations resulting in upward forces and cell elimination. We show how a winning cell type endowed with a stronger intercellular adhesion exhibits higher resistance to elimination and benefiting from efficient force transmission to the neighbouring cells. This cell elimination mechanism could have broad implications for keeping the strong force transmission ability for maintaining tissue boundaries and cell invasion pathology.
细胞竞争是一种消除不需要细胞的组织监测机制,在发育、感染和肿瘤发生过程中不可或缺。尽管研究已经确定了生化机制在这一过程中的作用,但由于在这些系统中测量力存在挑战,机械力如何决定竞争结果仍不清楚。在这里,我们报告了一种由力传递能力差异调节的细胞竞争形式,选择具有更强细胞间粘附力的细胞类型。对离体组织和不同细胞系的直接力测量表明,在两种竞争细胞类型之间的界面处机械活性增加,这可能导致大的应力波动,从而产生向上的力并导致细胞消除。我们展示了具有更强细胞间粘附力的获胜细胞类型如何表现出更高的抗消除能力,并受益于向邻近细胞的有效力传递。这种细胞消除机制可能对维持组织边界和细胞侵袭病理学的强大力传递能力具有广泛影响。