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首页> 外文期刊>Biomaterials Science >A peptide functionalized poly(ethylene glycol) (PEG) hydrogel for investigating the influence of biochemical and biophysical matrix properties on tumor cell migration
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A peptide functionalized poly(ethylene glycol) (PEG) hydrogel for investigating the influence of biochemical and biophysical matrix properties on tumor cell migration

机译：肽功能化聚乙二醇（PEG）水凝胶，用于研究生化和生物物理基质性质对肿瘤细胞迁移的影响

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摘要

To address the challenges associated with defined control over matrix properties in 3D cell culture systems, we employed a peptide functionalized poly(ethylene glycol) (PEG) hydrogel matrix in which mechanical modulus and adhesive properties were tuned. An HT-1080 human fibrosarcoma cell line was chosen as a model for probing matrix influences on tumor cell migration using the PEG hydrogel platform. HT-1080 speed varied with a complex dependence on both matrix modulus and Cys-Arg-Gly-Asp-Ser (CRGDS) adhesion ligand concentration, with regimes in which motility increased, decreased, or was minimally altered being observed. We further investigated cell motility by forming matrix interfaces that mimic aspects of tissue boundaries that might be encountered during invasion by taking advantage of the spatial control of the thiol-ene photochemistry to form patterned regions of low and high cross-linking densities. HT-1080s in 100 Pa regions of patterned PEG hydrogels tended to reverse direction or aggregate at the interface when they encountered a 360 Pa boundary. In contrast, HT-1080s were apparently unimpeded when migrating from the stiff to the soft regions of PEG peptide hydrogels, which may indicate that cells are capable of "reverse durotaxis" within at least some matrix regimes. Taken together, our results identified matrix regimes in which HT-1080 motility was both positively and negatively influenced by cell adhesion or matrix modulus.
机译：为了解决与在3D细胞培养系统中对基质特性进行定义控制相关的挑战，我们采用了肽官能化的聚乙二醇（PEG）水凝胶基质，在其中调节了机械模量和粘合性能。选择HT-1080人纤维肉瘤细胞系作为模型，使用PEG水凝胶平台探测基质对肿瘤细胞迁移的影响。 HT-1080速度随基质模量和Cys-Arg-Gly-Asp-Ser（CRGDS）粘附配体浓度的复杂依赖性而变化，观察到运动性增加，降低或变化最小的机制。我们通过形成基质界面来研究细胞运动，该界面模拟通过利用硫醇-烯光化学的空间控制形成低交联密度和高交联密度的图案化区域来模拟入侵过程中可能遇到的组织边界方面。当图案化PEG水凝胶的100 Pa区域中的HT-1080遇到360 Pa边界时，趋向于反向或聚集在界面上。相反，从PEG肽水凝胶的刚性区域迁移到软区域时，HT-1080显然不受阻碍，这可能表明细胞能够在至少某些基质体系中“逆转durotaxis”。两者合计，我们的结果确定了基质方案，其中HT-1080运动受细胞粘附或基质模量的正负影响。

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