Biomedical Sciences Program, College of Health Sciences, Midwestern University, Glendale, AZ 85308, United States.
Department of Microbiology & Immunology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ 85308, United States.
Exp Cell Res. 2014 Aug 1;326(1):155-65. doi: 10.1016/j.yexcr.2014.06.011. Epub 2014 Jun 26.
Fish keratocytes are an established model in single cell motility but little is known about their collective migration. Initially, sheets migrate from the scale at ~145 μm/h but over the course of 24h the rate of leading edge advance decreases to ~23 μm/h. During this period, leader cells retain their ability to migrate rapidly when released from the sheet and follower cell area increases. After the addition of RGD peptide, leader cell lamellae are lost, altering migratory forces within the sheet, resulting in rapid retraction. Leader and follower cell states interconvert within minutes with changes in cell-cell adhesions. Leader cells migrate as single cells when they detach from the leading edge and single cells appear to become leader cells if they rejoin the sheet. Follower cells rapidly establish leader cell morphology during closing of holes formed during sheet expansion and revert to follower cell morphology after hole-closure. Inhibition of Rho associated kinase releases leader cells and halts advancement of the leading edge suggesting an important role for the intercellular actomyosin cable at the leading edge. In addition, the presence of the stationary scale orients direction of sheet migration which is characterized by a more uniform advance of the leading edge than in some cell line systems. These data establish fish keratocyte explant cultures as a collective cell migration system and suggest that cell-cell interactions determine the role of keratocytes within the migrating sheet.
鱼类角膜细胞是单细胞迁移的成熟模型，但对其集体迁移知之甚少。最初，薄片以约 145 μm/h 的速度从鳞片迁移，但在 24 小时的过程中，前沿的前进速度下降到约 23 μm/h。在此期间，当从薄片中释放时，先导细胞保持快速迁移的能力，并且跟随细胞区域增加。在添加 RGD 肽后，先导细胞薄片丢失，改变了薄片内的迁移力，导致快速收缩。在细胞-细胞黏附力发生变化的几分钟内，先导细胞和跟随细胞状态发生转换。当先导细胞从前沿脱离时，它们作为单细胞迁移，并且如果它们重新加入薄片，则单细胞似乎成为先导细胞。当薄片扩展形成孔时，跟随细胞迅速建立先导细胞形态，并在孔闭合后恢复为跟随细胞形态。Rho 相关激酶的抑制释放先导细胞并停止前沿的推进，这表明在前沿的细胞间肌动球蛋白电缆起着重要作用。此外，静止鳞片的存在确定了薄片迁移的方向，其特征是前沿的推进更均匀，而不是在一些细胞系系统中。这些数据确立了鱼类角膜细胞外植体培养作为一个集体细胞迁移系统，并表明细胞-细胞相互作用决定了角膜细胞在迁移薄片中的作用。
