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Macromolecular crowding tunes 3D collagen architecture and cell morphogenesis

机译:大分子挤压曲调3D胶原型建筑和细胞形态发生

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摘要

Collagen I is the primary extracellular matrix component of most solid tumors and influences metastatic progression. Collagen matrix engineering techniques are useful for understanding how this complex biomaterial regulates cancer cell behavior and for improving in vitro cancer models. Here, we establish an approach to tune collagen fibril architecture using PEG as an inert molecular crowding agent during gelation and cell embedding. We find that crowding produces matrices with tighter fibril networks that are less susceptible to proteinase mediated degradation, but does not significantly alter matrix stiffness. The resulting matrices have the effect of preventing cell spreading, confining cells, and reducing cell contractility. Matrix degradability and fibril length are identified as strong predictors of cell confinement. Further, the degree of confinement predicts whether breast cancer cells will ultimately undergo individual or collective behaviors. Highly confined breast cancer cells undergo morphogenesis to form either invasive networks reminiscent of aggressive tumors or gland and lobule structures reminiscent of normal breast epithelia. This morphological transition is accompanied by expression of cell-cell adhesion genes, including PECAM1 and ICAM1. Our study suggests that cell confinement, mediated by matrix architecture, is a design feature that tunes the transcriptional and morphogenic state of breast cancer cells.
机译:胶原蛋白I是大多数固体瘤的主要细胞外基质组分,影响转移性进展。胶原素矩阵工程技术对于理解这种复杂的生物材料如何调节癌细胞行为以及改善体外癌症模型的有用是有用的。在这里,我们建立一种在胶凝和细胞嵌入期间使用PEG作为惰性分子挤压剂调谐胶原纤维架构的方法。我们发现拥挤产生具有更严重的纤维网络的矩阵,所述纤维网络不易易受蛋白酶介导的降解,但不会显着改变基质刚度。所得基质具有防止细胞扩散,限制细胞和减少细胞收缩性的效果。基质可降解性和原纤维长度被鉴定为细胞监禁的强预测因子。此外,限制程度预测乳腺癌细胞是否最终会接受个体或集体行为。高度限制的乳腺癌细胞经历了形态发生,以形成任何侵入性网络,让人想起激进的肿瘤或腺体和鳞状结构让人想起正常乳腺上皮。这种形态转变伴有细胞 - 细胞粘附基因的表达,包括PECAM1和ICAM1。我们的研究表明,由矩阵架构介导的细胞限制是一种设计特征,其调整乳腺癌细胞的转录和形态发生状态。

著录项

  • 来源
    《Biomaterials Science》 |2019年第2期|共16页
  • 作者单位

    Univ Calif San Diego Jacobs Sch Engn Bioengn La Jolla CA 92093 USA;

    Univ Calif San Diego Jacobs Sch Engn Bioengn La Jolla CA 92093 USA;

    Univ Calif San Diego Jacobs Sch Engn Bioengn La Jolla CA 92093 USA;

    Univ Calif San Diego Jacobs Sch Engn Bioengn La Jolla CA 92093 USA;

    Univ Calif San Diego Jacobs Sch Engn Bioengn La Jolla CA 92093 USA;

    Univ Calif San Diego Jacobs Sch Engn Bioengn La Jolla CA 92093 USA;

    Univ Calif San Diego Jacobs Sch Engn Bioengn La Jolla CA 92093 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子生物学;
  • 关键词

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