Cell movement is guided by the rigidity of the substrate

Cell movement is guided by the rigidity of the substrate
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DOI:
10.1016/s0006-3495(00)76279-5
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发表时间:
2000-07-01
影响因子:
3.4
通讯作者:
Wang, YL
Wang, YL
中科院分区:
生物学3区
文献类型:
--
作者:
Lo, CM;Wang, HB;Wang, YL

文献摘要

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细胞的定向运动在许多生理过程中都是至关重要的,包括形态发生、免疫反应和伤口愈合。众所周知,在这些过程中,细胞的运动可以由各种化学信号的梯度来引导。在这项研究中,我们证明了细胞运动也可以由细胞-底物界面上的纯物理相互作用来指导。我们在涂有I型胶原的聚丙烯酰胺软片上培养了美国国立卫生研究院3T3成纤维细胞。通过双丙烯酰胺交联剂浓度的不连续,在片材的中心区域引入了刚性转变。从软边靠近过渡区的细胞可以很容易地跨越边界迁移,同时扩展面积和牵引力也会增加。相反,从僵硬一侧迁移的细胞在到达边界时会掉头或回缩。我们把这种对硬质底物的明显偏好称为“趋杜性”。除了基质的刚性,我们还发现,通过操纵柔性基质在极化细胞的前部或后部产生机械应变,也可以引导细胞的运动。我们得出结论,组织刚性和应变的变化可能在涉及细胞运动的许多正常和病理过程中发挥重要的控制作用。
Directional cell locomotion is critical in many physiological processes, including morphogenesis, the immune response, and wound healing. It is well known that in these processes cell movements can be guided by gradients of various chemical signals. In this study, we demonstrate that cell movement can also be guided by purely physical interactions at the cell-substrate interface. We cultured National Institutes of Health 3T3 fibroblasts on flexible polyacrylamide sheets coated with type I collagen. A transition in rigidity was introduced in the central region of the sheet by a discontinuity in the concentration of the bis-acrylamide cross-linker. Cells approaching the transition region from the soft side could easily migrate across the boundary, with a concurrent increase in spreading area and traction forces. in contrast, cells migrating from the stiff side turned around or retracted as they reached the boundary. We call this apparent preference for a stiff substrate "durotaxis." In addition to substrate rigidity, we discovered that cell movement could also be guided by manipulating the flexible substrate to produce mechanical strains in the front or rear of a polarized cell. We conclude that changes in tissue rigidity and strain could play an important controlling role in a number of normal and pathological processes involving cell locomotion.