德国马普所Ricard Alert、西班牙巴塞罗那大学Raimon Sunyer和Jaume Casademunt以及西班牙加泰罗尼亚生物工程研究所Xavier Trepat研究小组发现，依赖于刚度的主动润湿能够实现最佳的集体细胞趋硬性。该项研究成果发表在2022年12月8日出版的《自然—物理学》上。

研究人员揭示了细胞集群的湿润特性与集体性趋硬性之间的联系。该团队发现癌细胞簇使软基质脱湿，而硬基质保湿。在中等硬度下，即从低润湿性到高润湿性的交叉点上，均匀硬度基底上，团簇变得最具运动性，而在硬度梯度上，团簇表现出最佳的趋硬性。趋硬性速度随着集群大小、硬度梯度和肌动蛋白活性的增加而增加。研究人员在涂有细胞-细胞粘附蛋白E-cadherin的底物上演示了这种行为，然后建立了其在涂有细胞外基质的底物上的普遍性。

研究人员开发了一个主动润湿模型，根据平面内主动牵引和组织收缩性以及平面外表面张力之间的平衡，解释了集体趋硬性。最后，研究人员表明，集群位移的分布有一个沉重的尾巴，有不经常出现但很大的细胞跳动，有助于硬膜定向迁移。他们的研究基于活性液滴的润湿特性，通过细胞-细胞和细胞-基质的粘附配体，证明了集体趋硬性的物理机制。

据了解，细胞团簇的定向迁移强化了形态发生、伤口愈合和聚集性癌症侵袭。基质硬度的梯度引导细胞团迁移，这一过程称之为集体趋硬性collective durotaxis，但其潜在机制尚不清楚。

附：英文原文

Title: Stiffness-dependent active wetting enables optimal collective cell durotaxis

Author: Pallars, Maci Esteve, Pi-Jaum, Irina, Fortunato, Isabela Corina, Grazu, Valeria, Gmez-Gonzlez, Manuel, Roca-Cusachs, Pere, de la Fuente, Jesus M., Alert, Ricard, Sunyer, Raimon, Casademunt, Jaume, Trepat, Xavier

Issue&Volume: 2022-12-08

Abstract: The directed migration of cellular clusters enables morphogenesis, wound healing and collective cancer invasion. Gradients of substrate stiffness direct the migration of cellular clusters in a process called collective durotaxis, but the underlying mechanisms remain unclear. Here we unveil a connection between collective durotaxis and the wetting properties of cellular clusters. We show that clusters of cancer cells dewet soft substrates and wet stiff ones. At intermediate stiffness—at the crossover from low to high wettability—clusters on uniform-stiffness substrates become maximally motile, and clusters on stiffness gradients exhibit optimal durotaxis. Durotactic velocity increases with cluster size, stiffness gradient and actomyosin activity. We demonstrate this behaviour on substrates coated with the cell–cell adhesion protein E-cadherin and then establish its generality on substrates coated with extracellular matrix. We develop an active wetting model that explains collective durotaxis in terms of a balance between in-plane active traction and tissue contractility and out-of-plane surface tension. Finally, we show that the distribution of cluster displacements has a heavy tail, with infrequent but large cellular hops that contribute to durotactic migration. Our study demonstrates a physical mechanism of collective durotaxis, through both cell–cell and cell–substrate adhesion ligands, based on the wetting properties of active droplets.

DOI: 10.1038/s41567-022-01835-1

Source: https://www.nature.com/articles/s41567-022-01835-1