Direct Comparisons of the Morphology, Migration, Cell Adhesions, and Actin Cytoskeleton of Fibroblasts in Four Different Three-Dimensional Extracellular Matrices
Direct Comparisons of the Morphology, Migration, Cell Adhesions, and Actin Cytoskeleton of Fibroblasts in Four Different Three-Dimensional Extracellular Matrices
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DOI：
10.1089/ten.tea.2010.0273
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发表时间：
2011-03-01
影响因子：
4.1
通讯作者：
Yamada, Kenneth M.
中科院分区：
文献类型：
--
作者：
Hakkinen, Kirsi M.;Harunaga, Jill S.;Yamada, Kenneth M.
细胞和细胞外基质之间的相互作用是组织工程和生物学的核心。然而，这些相互作用的大多数研究都使用传统的二维（2D）组织培养，这是比三维（3D）组织培养生理。在这项研究中，我们比较了细胞在2D和3D条件下在四种常用细胞外基质中的行为。具体而言，我们量化了细胞粘附和迁移的参数，人包皮成纤维细胞在细胞衍生的基质或水凝胶的胶原蛋白I型，纤维蛋白，或基底膜提取物（BME）。3D中的成纤维细胞比2D基质更呈纺锤形，具有更少的侧向突起和显著减少的肌动蛋白应力纤维;细胞未能在3D BME中扩散。在所有基质中检测到细胞-基质粘附结构。虽然这些细胞粘附的形状不同，但2D和3D中细胞-基质粘附所占据的每个细胞的总面积几乎相同。成纤维细胞在细胞衍生的3D基质和胶原中迁移最快，在BME中迁移最少，在细胞衍生的基质中迁移方向性最高。这种对不同基质组成和维度的细胞反应的定量差异的识别应该有助于指导定制的3D组织培养和组织工程基质支架的开发。
Interactions between cells and the extracellular matrix are at the core of tissue engineering and biology. However, most studies of these interactions have used traditional two-dimensional (2D) tissue culture, which is less physiological than three-dimensional (3D) tissue culture. In this study, we compared cell behavior in four types of commonly used extracellular matrix under 2D and 3D conditions. Specifically, we quantified parameters of cell adhesion and migration by human foreskin fibroblasts in cell-derived matrix or hydrogels of collagen type I, fibrin, or basement membrane extract (BME). Fibroblasts in 3D were more spindle shaped with fewer lateral protrusions and substantially reduced actin stress fibers than on 2D matrices; cells failed to spread in 3D BME. Cell-matrix adhesion structures were detected in all matrices. Although the shapes of these cell adhesions differed, the total area per cell occupied by cell-matrix adhesions in 2D and 3D was nearly identical. Fibroblasts migrated most rapidly in cell-derived 3D matrix and collagen and migrated minimally in BME, with highest migration directionality in cell-derived matrix. This identification of quantitative differences in cellular responses to different matrix composition and dimensionality should help guide the development of customized 3D tissue culture and matrix scaffolds for tissue engineering.