Biophysical control of invasive tumor cell behavior by extracellular matrix microarchitecture.
Biophysical control of invasive tumor cell behavior by extracellular matrix microarchitecture.
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DOI：
10.1016/j.biomaterials.2012.02.029
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发表时间：
2012-06
期刊：
影响因子：
14
通讯作者：
Reinhart-King, Cynthia A.
中科院分区：
文献类型：
--
作者：
Carey, Shawn P.;Kraning-Rush, Casey M.;Williams, Rebecca M.;Reinhart-King, Cynthia A.
关键词：
纤维状胶原凝胶广泛用于体外研究肿瘤-微环境相互作用，由相互连接的纤维和孔的细胞指导网络组成，其组织对聚合条件（例如体积浓度、pH 值和温度）敏感。使用共焦反射显微镜和图像自相关分析来定量评估凝胶微结构，我们表明，包括培养基配方和凝胶厚度在内的其他聚合参数显着影响胶原凝胶中纤维和孔的尺寸和组织。这些发现使得三维培养系统的开发成为可能，其中细胞规模的凝胶微结构与散装凝胶胶原蛋白浓度分离。有趣的是，嵌入的 MDA-MB-231 细胞的形态和迁移特征对凝胶微结构敏感，与胶原凝胶浓度无关。无论凝胶体积密度如何，细胞在具有较大纤维和孔的凝胶中采用极化的运动表型，在具有小纤维和孔的凝胶中采用圆形或星形、运动性较差的表型。相反，细胞增殖对凝胶浓度敏感，但对微结构不敏感。这些结果表明，细胞规模的凝胶微结构在控制特定细胞行为方面可能胜过体积规模的凝胶密度，强调了凝胶微结构在影响细胞行为中的生物物理作用。
Fibrillar collagen gels, which are used extensively in vitro to study tumor-microenvironment interactions, are composed of a cell-instructive network of interconnected fibers and pores whose organization is sensitive to polymerization conditions such as bulk concentration, pH, and temperature. Using confocal reflectance microscopy and image autocorrelation analysis to quantitatively assess gel microarchitecture, we show that additional polymerization parameters including culture media formulation and gel thickness significantly affect the dimensions and organization of fibers and pores in collagen gels. These findings enabled the development of a three-dimensional culture system in which cell-scale gel microarchitecture was decoupled from bulk gel collagen concentration. Interestingly, morphology and migration characteristics of embedded MDA-MB-231 cells were sensitive to gel microarchitecture independently of collagen gel concentration. Cells adopted a polarized, motile phenotype in gels with larger fibers and pores and a rounded or stellate, less motile phenotype in gels with small fibers and pores regardless of bulk gel density. Conversely, cell proliferation was sensitive to gel concentration but not microarchitecture. These results indicate that cell-scale gel microarchitecture may trump bulk-scale gel density in controlling specific cell behaviors, underscoring the biophysical role of gel microarchitecture in influencing cell behavior.
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