近日，西班牙巴塞罗那科学技术学院(BIST)的Xavier Trepat&Leone Rossetti及其研究小组与德国马克斯普朗克复杂系统物理研究所的Ricard Alert等人合作并取得一项新进展。经过不懈努力，他们发现先导细胞的光遗传产生揭示了集体细胞迁移的力-速度关系。相关研究成果已于2024年8月12日在国际知名学术期刊《自然—物理学》上发表。
本文表明，先导-跟随者组织的效能与细胞群内的牵引力和张力的不对称性成正比。通过结合水凝胶微缩成像和光遗传学激活技术，研究人员在最小细胞群的边缘生成了高度突出的先导细胞。研究发现，诱导产生的先导细胞能够稳健地拖动一个跟随者，但无法拖动更大的群体。
通过测量不同大小的细胞群中的牵引力和张力传播，研究人员建立了群体速度与牵引力和张力分布不对称性之间的定量关系。研究人员将运动细胞群建模为活性极性流体，并从活性牵引力分布的不对称性角度解释了这种力与速度的关系。这项研究结果对自主先导细胞的概念提出了挑战，表明集体细胞迁移需要细胞群内的全局机械组织。
据悉，在发育、伤口愈合和癌症侵袭过程中，迁移的细胞群会在其前端形成高度突出的先导细胞。人们认为先导细胞会拉动并指导其跟随者，但关于其局部作用是否足以引导整个细胞群，或者是否需要全局性的机械组织，仍存在争议。
附：英文原文
Title: Optogenetic generation of leader cells reveals a force–velocity relation for collective cell migration
Author: Rossetti, Leone, Grosser, Steffen, Abenza, Juan Francisco, Valon, Lo, Roca-Cusachs, Pere, Alert, Ricard, Trepat, Xavier
Issue&Volume: 2024-08-12
Abstract: During development, wound healing and cancer invasion, migrating cell clusters feature highly protrusive leader cells at their front. Leader cells are thought to pull and direct their cohort of followers, but whether their local action is enough to guide the entire cluster, or if a global mechanical organization is needed, remains controversial. Here we show that the effectiveness of the leader–follower organization is proportional to the asymmetry of traction and tension within cell clusters. By combining hydrogel micropatterning and optogenetic activation, we generate highly protrusive leaders at the edge of minimal cell clusters. We find that the induced leader can robustly drag one follower but not larger groups. By measuring traction forces and tension propagation in clusters of increasing size, we establish a quantitative relationship between group velocity and the asymmetry of the traction and tension profiles. Modelling motile clusters as active polar fluids, we explain this force–velocity relationship in terms of asymmetries in the active traction profile. Our results challenge the notion of autonomous leader cells, showing that collective cell migration requires global mechanical organization within the cluster.
DOI: 10.1038/s41567-024-02600-2
Source: https://www.nature.com/articles/s41567-024-02600-2