论文标题
纤维肉瘤细胞中的手性边缘电流
Chiral edge currents in confined fibrosarcoma cells
论文作者
论文摘要
在转移性传播过程中,细胞流在进入血流之前,通过细胞外基质内的狭窄通道网络共同迁移。基于观察到,单个癌细胞可以利用限制来切换到无依赖的运动形式的观察结果,该策略被认为优于其他迁移模式。然而,这种行为的物理起源仍然难以捉摸,目前尚不清楚入侵细胞种群中相干流的出现背后的机制。在这里,我们证明了狭窄条带形区域限制在狭窄条纹区域中的人纤维肉瘤细胞(HT1080)通过一种新型的拓扑边缘电流进行集体迁移,这是由于液体晶体(nematic)秩序,显微镜芯干和拓扑缺陷之间的相互作用所致。多亏了体外实验和主动流体动力学理论的结合,我们表明,虽然在通道的大部分中,异质性和混乱,但在HT1080细胞的密闭种群中产生的自发流沿着边缘进行了整流,导致了长期的集体细胞迁移,并具有损坏的细胞迁移。这些边缘电流由+1/2拓扑缺陷的层燃料,正交锚定在通道墙,并充当手性活动应力的局部来源。我们的工作强调了多细胞系统中的限制与集体迁移之间的密切相关性,并提出了转移性癌症中定向运动的可能机制。
During metastatic dissemination, streams of cells collectively migrate through a network of narrow channels within the extracellular matrix, before entering into the blood stream. This strategy is believed to outperform other migration modes, based on the observation that individual cancer cells can take advantage of confinement to switch to an adhesion-independent form of locomotion. Yet, the physical origin of this behaviour has remained elusive and the mechanisms behind the emergence of coherent flows in populations of invading cells under confinement are presently unknown. Here we demonstrate that human fibrosarcoma cells (HT1080) confined in narrow stripe-shaped regions undergo collective migration by virtue of a novel type of topological edge currents, resulting from the interplay between liquid crystalline (nematic) order, microscopic chirality and topological defects. Thanks to a combination of in vitro experiments and theory of active hydrodynamics, we show that, while heterogeneous and chaotic in the bulk of the channel, the spontaneous flow arising in confined populations of HT1080 cells is rectified along the edges, leading to long-ranged collective cell migration, with broken chiral symmetry. These edge currents are fuelled by layers of +1/2 topological defects, orthogonally anchored at the channel walls and acting as local sources of chiral active stress. Our work highlights the profound correlation between confinement and collective migration in multicellular systems and suggests a possible mechanism for the emergence of directed motion in metastatic cancer.