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首页> 外文期刊>Biomaterials Science >Biomaterial arrays with defined adhesion ligand densities and matrix stiffness identify distinct phenotypes for tumorigenic and non-tumorigenic human mesenchymal cell types
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Biomaterial arrays with defined adhesion ligand densities and matrix stiffness identify distinct phenotypes for tumorigenic and non-tumorigenic human mesenchymal cell types

机译：具有确定的粘附配体密度和基质刚度的生物材料阵列可确定致瘤性和非致瘤性人间充质细胞类型的不同表型

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Here, we aimed to investigate migration' of a model tumor cell line (HT-1080 fibrosarcoma cells, HT-1080s) using synthetic biomaterials to systematically vary peptide ligand density and substrate stiffness. A range of substrate elastic moduli were investigated by using poly(ethylene glycol) (PEG) hydrogel arrays (0.34-17 kPa) and self-assembled monolayer (SAM) arrays (～0.1-1 GPa), while cell adhesion was tuned by varying the presentation of Arg-Gly-Asp (RGD)-containing peptides. HT-1080 motility was insensitive to cell adhesion ligand density on RGD-SAMs, as they migrated with similar speed and directionality for a wide range of RGD densities (0.2-5% mol fraction RGD). Similarly, HT-1080 migration speed was weakly dependent on adhesion on 0.34 kPa PEG surfaces. On 13 kPa surfaces, a sharp initial increase in cell speed was observed at low RGD concentration, with no further changes observed as RGD concentration was increased further. An increase in cell speed ～two-fold for the 13 kPa relative to the 0.34 kPa PEG surface suggested an important role for substrate stiffness in mediating motility, which was confirmed for HT-1080s migrating on variable modulus PEG hydrogels with constant RGD concentration. Notably, despite ～two-fold changes in cell speed over a wide range of moduli, HT-1080s adopted rounded morphologies on all surfaces investigated, which contrasted with well spread primary human mesenchymal stem cells (hMSCs). Taken together, our results demonstrate that HT-1080s are morphologically distinct from primary mesenchymal cells (hMSCs) and migrate with minimal dependence on cell adhesion for surfaces within a wide range of moduli, whereas motility is strongly influenced by matrix mechanical properties.
机译：在这里，我们旨在研究使用合成生物材料系统地改变肽配体密度和底物硬度的模型肿瘤细胞系（HT-1080纤维肉瘤细胞，HT-1080s）的迁移。通过使用聚乙二醇（PEG）水凝胶阵列（0.34-17 kPa）和自组装单层（SAM）阵列（〜0.1-1 GPa）研究了一系列的基质弹性模量，同时通过改变细胞粘附力来调节含Arg-Gly-Asp（RGD）肽的展示。 HT-1080的运动性对RGD-SAMs上的细胞粘附配体密度不敏感，因为它们以相似的速度和方向迁移了各种RGD密度（0.2-5％摩尔分数RGD）。同样，HT-1080的迁移速度微弱地依赖于在0.34 kPa PEG表面上的附着力。在13 kPa的表面上，在低RGD浓度下观察到了细胞速度的初始急剧增加，而随着RGD浓度的进一步增加，没有观察到进一步的变化。相对于0.34 kPa PEG表面，13 kPa的细胞速度提高了两倍左右，这表明底物刚度在介导运动性中起着重要作用，这一点已被HT-1080s在恒定RGD浓度的可变模量PEG水凝胶上迁移证实。值得注意的是，尽管在广泛的模量范围内细胞速度发生了约两倍的变化，但HT-1080s在所研究的所有表面上均采用了圆形形态，这与散布良好的原代人间充质干细胞（hMSCs）形成了鲜明对比。两者合计，我们的结果表明HT-1080s在形态上与原代间充质细胞（hMSCs）不同，并且在很宽的模量范围内以对细胞粘附的最小依赖性迁移，而运动性受基质机械性能的强烈影响。

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