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3D organizational mapping of collagen fibers elucidates matrix remodeling in a hormone-sensitive 3D breast tissue model.
Biomaterials ( IF 14.0 ) Pub Date : 2018-06-26 , DOI: 10.1016/j.biomaterials.2018.06.036
Zhiyi Liu 1 , Lucia Speroni 2 , Kyle P Quinn 3 , Carlo Alonzo 4 , Dimitra Pouli 4 , Yang Zhang 4 , Emily Stuntz 4 , Carlos Sonnenschein 2 , Ana M Soto 2 , Irene Georgakoudi 4
Affiliation  

Hormones play an important role in normal and diseased breast tissue development. However, they can also disrupt cell-matrix interactions and their role in extracellular matrix reorganization during epithelial morphogenesis remains poorly understood, partly due to a lack of sensitive approaches for matrix characterization. Here, we assess the hormonal regulation of matrix reorganization in a three-dimensional (3D) breast tissue culture model using a novel metric, i.e., 3D directional variance, to characterize the 3D organization of collagen fibers visualized via high-resolution, second harmonic generation imaging. This metric enables resolving and quantifying patterns of spatial organization throughout the matrix surrounding epithelial structures treated with 17β-estradiol (E2) alone, and E2 in combination with either promegestone, a progestogen, or prolactin. Addition of promegestone results in the most disorganized fibers, while the E2 alone treatment leads to the most organized ones. Location-dependent organization mapping indicates that only the prolactin treatment leads to significant heterogeneities in the regional organization of collagen fibers, with higher levels of alignment observed at the end of the elongated epithelial structures. The observed collagen organization patterns for all groups persist for tens of micrometers. In addition, a comparison between 3D directional variance and typical 2D analysis approaches reveals an improved sensitivity of the 3D metric to identify organizational heterogeneities and differences among treatment groups. These results demonstrate that 3D directional variance is sensitive to subtle changes in the extracellular micro-environment and has the potential to elucidate reciprocal cell-matrix interactions in the context of numerous applications involving the study of normal and diseased tissue morphogenesis.

中文翻译:

胶原纤维的3D组织映射可阐明激素敏感的3D乳房组织模型中的基质重塑。

激素在正常和患病的乳房组织发育中起重要作用。然而,它们还可能破坏细胞-基质相互作用,并且在上皮形态发生过程中它们在细胞外基质重组中的作用仍然知之甚少,部分原因是缺乏用于基质表征的敏感方法。在这里,我们使用新的度量标准(即3D方向方差)评估三维(3D)乳房组织培养模型中基质重组的激素调节,以表征通过高分辨率,二次谐波产生可视化的胶原纤维的3D组织成像。通过该指标,可以解析和量化整个单独用17β-雌二醇(E2)和E2与Progegestone,孕激素,或催乳素。加入Promegestone会导致纤维最混乱,而仅E2处理会导致纤维最有组织。依赖位置的组织作图表明,只有催乳激素治疗会导致胶原纤维区域组织中的显着异质性,并且在伸长的上皮结构末端观察到更高水平的比对。所有组观察到的胶原组织模式持续数十微米。此外,在3D方向方差与典型2D分析方法之间的比较显示,提高了3D指标识别组织异质性和治疗组之间差异的敏感性。
更新日期:2018-06-27
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