Peptide gels of fully-defined composition and mechanics for probing cell-cell and cell-matrix interactions in vitro.
Peptide gels of fully-defined composition and mechanics for probing cell-cell and cell-matrix interactions in vitro.
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DOI：
10.1016/j.matbio.2019.06.009
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发表时间：
2020-01
期刊：
影响因子：
--
通讯作者：
Merry CLR
中科院分区：
文献类型：
--
作者：
Ashworth JC;Thompson JL;James JR;Slater CE;Pijuan-Galitó S;Lis-Slimak K;Holley RJ;Meade KA;Thompson A;Arkill KP;Tassieri M;Wright AJ;Farnie G;Merry CLR
目前用于体外3D细胞培养的材料通常受到其与人体组织的相似性差、批次间差异性以及组成和制造复杂性的限制。在这里，我们提出了一个“白板”的文化环境的基础上自组装肽凝胶从矩阵图案。凝胶可以通过掺入选择匹配靶组织的基质组分来定制，并独立控制机械性能。因此，基质组分仅限于专门添加的那些或由包封细胞合成的那些。灵活的3D培养平台提供对生化和物理特性的完全控制，允许在体外单独评估生化成分和组织力学的影响。在这里，我们证明了肽凝胶支持一系列细胞的生长，包括人诱导多能干细胞和人癌细胞系。此外，我们提出了概念验证，肽凝胶可用于建立疾病相关模型。控制肽胶凝剂浓度允许肽凝胶硬度与正常乳腺（<1 kPa）或乳腺肿瘤组织（>1 kPa）匹配，其中较高的硬度有利于乳腺癌细胞的活力超过正常乳腺细胞。平行地，肽凝胶可以用与人乳房相关的基质组分如胶原蛋白I和透明质酸修饰。这些添加物的选择和浓度影响与成纤维细胞共培养中形成的乳腺上皮细胞结构的大小、形状和组织。因此，该系统提供了一种解开癌症和其他疾病中基质、机械性质和细胞-细胞相互作用的个体影响的手段。
Current materials used for in vitro 3D cell culture are often limited by their poor similarity to human tissue, batch-to-batch variability and complexity of composition and manufacture. Here, we present a “blank slate” culture environment based on a self-assembling peptide gel free from matrix motifs. The gel can be customised by incorporating matrix components selected to match the target tissue, with independent control of mechanical properties. Therefore the matrix components are restricted to those specifically added, or those synthesised by encapsulated cells. The flexible 3D culture platform provides full control over biochemical and physical properties, allowing the impact of biochemical composition and tissue mechanics to be separately evaluated in vitro. Here, we demonstrate that the peptide gels support the growth of a range of cells including human induced pluripotent stem cells and human cancer cell lines. Furthermore, we present proof-of-concept that the peptide gels can be used to build disease-relevant models. Controlling the peptide gelator concentration allows peptide gel stiffness to be matched to normal breast (<1 kPa) or breast tumour tissue (>1 kPa), with higher stiffness favouring the viability of breast cancer cells over normal breast cells. In parallel, the peptide gels may be modified with matrix components relevant to human breast, such as collagen I and hyaluronan. The choice and concentration of these additions affect the size, shape and organisation of breast epithelial cell structures formed in co-culture with fibroblasts. This system therefore provides a means of unravelling the individual influences of matrix, mechanical properties and cell-cell interactions in cancer and other diseases.
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影响因子：
16.6
作者：
Ferreira-Gonzalez S;Lu WY;Raven A;Dwyer B;Man TY;O'Duibhir E;Lewis PJS;Campana L;Kendall TJ;Bird TG;Tarrats N;Acosta JC;Boulter L;Forbes SJ
通讯作者：
Forbes SJ
影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
通讯作者：
Brugge, JS
影响因子：
56.9
作者：
Cukierman, E;Pankov, R;Yamada, KM
通讯作者：
Yamada, KM
影响因子：
7
作者：
Hansen, Kirk C.;Kiemele, Lauren;Schedin, Pepper
通讯作者：
Schedin, Pepper
影响因子：
11.2
作者：
Hwang, Rosa F.;Moore, Todd;Logsdon, Craig D.
通讯作者：
Logsdon, Craig D.