Membrane Nanowaves in Single and Collective Cell Migration

We report the characterization of three-dimensional membrane waves for migrating single and collective cells and describe their propagation using wide-field optical profiling technique with nanometer resolution. We reveal the existence of small and large membrane waves the amplitudes of which are in the range of ∼3–7 nm to ∼16–25 nm respectively, through the cell. For migrating single-cells, the amplitude of these waves is about 30 nm near the cell edge. Two or more different directions of propagation of the membrane nanowaves inside the same cell can be observed. After increasing the migration velocity by BMP-2 treatment, only one wave direction of propagation exists with an increase in the average amplitude (more than 80 nm near the cell edge). Furthermore for collective-cell migration, these membrane nanowaves are attenuated on the leader cells and poor transmission of these nanowaves to follower cells was observed. After BMP-2 treatment, the membrane nanowaves are transmitted from the leader cell to several rows of follower cells. Surprisingly, the vast majority of the observed membrane nanowaves is shared between the adjacent cells. These results give a new view on how single and collective-cells modulate their motility. This work has significant implications for the therapeutic use of BMPs for the regeneration of skin tissue.本研究报道了迁移状态下单个细胞与集体细胞的三维细胞膜波（membrane waves）特征，并采用纳米分辨率宽场光学形貌表征技术（wide-field optical profiling technique）对其传播过程进行了描述。研究发现细胞内存在大小两类细胞膜波，其振幅分别约为3~7 nm与16~25 nm。对于迁移中的单个细胞，这类膜波在细胞边缘附近的振幅约为30 nm。在同一个细胞内部，可观测到膜纳米波（membrane nanowaves）存在两种及以上不同的传播方向。经骨形态发生蛋白2（BMP-2）处理提升细胞迁移速度后，仅存在单一的膜波传播方向，且平均振幅升高（细胞边缘附近可达80 nm以上）。此外在集体细胞迁移过程中，这类膜纳米波在领头细胞中会发生衰减，且难以传递至跟随细胞。经骨形态发生蛋白2（BMP-2）处理后，膜纳米波可从领头细胞传递至数排跟随细胞。令人意外的是，观测到的绝大多数膜纳米波会在相邻细胞间共享。上述研究结果为解析单个细胞与集体细胞如何调控自身运动能力提供了全新视角。本研究对于骨形态发生蛋白家族（BMPs）在皮肤组织再生治疗中的应用具有重要指导意义。