Engineering strategies to recapitulate epithelial morphogenesis within synthetic three-dimensional extracellular matrix with tunable mechanical properties.
Engineering strategies to recapitulate epithelial morphogenesis within synthetic three-dimensional extracellular matrix with tunable mechanical properties.
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DOI：
10.1088/1478-3975/8/2/026013
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发表时间：
2011-04
期刊：
影响因子：
2
通讯作者：
Weaver VM
中科院分区：
文献类型：
--
作者：
Miroshnikova YA;Jorgens DM;Spirio L;Auer M;Sarang-Sieminski AL;Weaver VM
细胞外基质（ECM）的机械特性（例如硬度）影响细胞命运和组织形态发生，并促进疾病进展。然而，我们对ECM刚性调节细胞行为和命运的机制的理解仍然是基本的。为了解决这个问题，已经使用了许多二维和三维（3D）水凝胶系统来探索ECM的机械性质对细胞行为的影响。不幸的是，这些系统中的许多具有有限的应用，因为当凝胶弹性变化时，纤维结构、纤维长度和/或孔径通常平行变化。在这里，我们描述了使用ECM吸附，合成，自组装肽凝胶（SAP），能够重演正常上皮腺泡形态发生和基因表达的三维背景。通过利用这些SAP凝胶可获得的粘弹性范围，以及它们在配体密度和孔径变化最小的情况下重建天然样ECM原纤维拓扑结构的能力，我们能够在非恶性乳腺上皮细胞（MEC）中重建正常与肿瘤样表型和基因表达模式。因此，该SAP水凝胶系统提供了能够在3D背景下独立评估ECM刚度和多细胞上皮表型之间的相互作用的第一可调系统。
The mechanical properties (e.g. stiffness) of the extracellular matrix (ECM) influence cell fate and tissue morphogenesis and contribute to disease progression. Nevertheless, our understanding of the mechanisms by which ECM rigidity modulates cell behavior and fate remains rudimentary. To address this issue, a number of two and three dimensional (3D) hydrogel systems have been used to explore the effects of mechanical properties of the ECM on cell behavior. Unfortunately, many of these systems have limited application because fiber architecture, adhesiveness and/or pore size often change in parallel when gel elasticity is varied. Here we describe the use of ECM-adsorbed, synthetic, self-assembling peptide gels (SAPs) that are able to recapitulate normal epithelial acini morphogenesis and gene expression in a 3D context. By exploiting the range of visco-elasticity attainable with these SAP gels, and their ability to recreate native-like ECM fibril topology with minimal variability in ligand density and pore size, we were able to reconstitute normal versus tumor-like phenotype and gene expression patterns in nonmalignant mammary epithelial cells (MECs). Accordingly, this SAP hydrogel system presents the first tunable system capable of independently assessing the interplay between ECM stiffness and multi-cellular epithelial phenotype in a 3D context.
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影响因子：
64.5
作者：
Choquet, D;Felsenfeld, DP;Sheetz, MP
通讯作者：
Sheetz, MP
影响因子：
14
作者：
Chung, Cindy;Beecham, Michael;Mauck, Robert L.;Burdick, Jason A.
通讯作者：
Burdick, Jason A.
DOI：
10.1073/pnas.93.8.3509
发表时间：
1996-04-16
影响因子：
11.1
作者：
Boudreau, N;Werb, Z;Bissell, MJ
通讯作者：
Bissell, MJ
DOI：
10.1083/jcb.200405004
发表时间：
2004-09-13
期刊：
The Journal of cell biology
影响因子：
--
作者：
Engler AJ;Griffin MA;Sen S;Bönnemann CG;Sweeney HL;Discher DE
通讯作者：
Discher DE
影响因子：
3.8
作者：
CIMA, LG;INGBER, DE;LANGER, R
通讯作者：
LANGER, R