Biochemical and mechanical extracellular matrix properties dictate mammary epithelial cell motility and assembly.
Biochemical and mechanical extracellular matrix properties dictate mammary epithelial cell motility and assembly.
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生化和机械的细胞外基质特性决定了乳腺上皮细胞运动和组装。
DOI：
10.1002/biot.201100188
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发表时间：
2012-03
影响因子：
4.7
通讯作者：
Hammer, Daniel A.
中科院分区：
文献类型：
--
作者：
Shebanova, Olga;Hammer, Daniel A.
关键词：
了解细胞迁移和细胞间相互作用是了解细胞侵袭的关键，细胞侵袭是乳腺癌进展的关键步骤。细胞外基质的生物化学和机械信号在细胞-基质和细胞-细胞相互作用中起着重要作用。我们已经通过实验测试了这些线索的综合影响，以更好地了解细胞运动，力的产生，细胞间的相互作用和组装在一个“体外”乳腺癌模型。MCF-10A非致瘤性乳腺上皮细胞在具有不同纤连蛋白配体浓度和聚丙烯酰胺凝胶硬度的表面上观察到。我们的数据表明，细胞速度在基质刚性和粘附性方面都是双相的。细胞迁移速度的最大值仅发生在基底刚度和配体密度的特定组合下。我们发现细胞间的相互作用降低了迁移速度。然而，细胞施加到基底上的牵引力随着两种线索线性增加，成对的细胞施加的最大牵引力高于单个细胞。力和运动性之间的关系表明，在单细胞速度没有观察到细胞对中的最大值。细胞-细胞粘附在弹性≤ 1250帕斯卡（Pa）的较软凝胶上变得非常有利，这意味着存在促进细胞-细胞粘附超过细胞-基质粘附的顺应性阈值。最后，在硬度类似于癌前乳腺组织的凝胶上，400 Pa，细胞经历多细胞组装并在二维表面上分裂成三维球形聚集体。
Understanding cell migration and cell-cell interactions are key to understanding cell invasion, a critical step in the progression of breast cancer. Biochemical and mechanical cues of the extracellular matrix have been shown to play important roles in cell-matrix and cell-cell interactions. We have experimentally tested the combined influence of these cues to better understand cell motility, force generation, cell-cell interaction and assembly in an ‘in vitro’ breast cancer model. MCF-10A non-tumorigenic mammary epithelial cells were observed on surfaces with varying fibronectin ligand concentration and polyacrylamide gel rigidity. Our data shows that cell velocity is biphasic in both matrix rigidity and adhesiveness. The maximum in cell migration velocity occurs only at specific combination of substrate stiffness and ligand density. We found cell-cell interactions reduce migration velocity. However the traction forces cells exert onto the substrate increase linearly with both cues, with cell in pairs exerting higher maximum tractions observed over single cells. A relationship between force and motility shows a maximum in single cell velocity not observed in cell pairs. Cell-cell adhesion becomes strongly favored on softer gels with elasticity ≤ 1250 Pascals (Pa), implying an existence of a compliance threshold that promotes cell-cell over cell-matrix adhesion. Finally on gels with stiffness similar to pre- malignant breast tissue, 400Pa, cells undergo multi-cellular assembly and division into three-dimensional spherical aggregates on a two-dimensional surface.
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