Substrate elasticity as biomechanical modulator of tissue homeostatic parameters in corneal keratinocytes.
Substrate elasticity as biomechanical modulator of tissue homeostatic parameters in corneal keratinocytes.
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DOI：
10.1016/j.yexcr.2013.05.002
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发表时间：
2013-07
影响因子：
3.7
通讯作者：
Katharina Moers;T. Steinberg;G. Schlunck;T. Reinhard;P. Tomakidi;P. Eberwein
中科院分区：
文献类型：
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作者：
Katharina Moers;T. Steinberg;G. Schlunck;T. Reinhard;P. Tomakidi;P. Eberwein
本研究旨在确定生物力学提示对角膜角质形成细胞内组织稳态参数的调节作用，为创新的角膜生物力学定制生物材料奠定基础。由于角膜上皮生物力学已经被描述为纳米结构上的接触，我们在这里分析了细胞对机械基质弹性的反应。因此，角膜角质形成细胞建立在生理相关的弹性底物上，也可以在1.74 Mpa的非生理性刚性底物上培养3天。定量聚合酶链式反应显示，基因表达的变化仅在40kPa130kPa之间，而在研究中的大多数组织固有生物标志物的1.74 Mpa底物上可以看到显著的调节。基因表达与蛋白质的表达相当一致，分化进程生物标记物总环蛋白和填充蛋白在40kPa和130kPa弹性之间已经显著增加。在局灶性粘连方面，在40kPa40~130kPa时，β1整合素和磷酸化p125FAK增强，而从130kPa时至1.74 Mpa时，肌动蛋白重新分布，磷酸化p125FAK显著上调。这些发现表明，弹性依赖于角膜角质形成细胞的分化进程和局部黏附动力学，支持生物力学支配组织稳态调节的概念。此外，这一概念反过来又可以转化为针对眼科治疗方法的预期角膜定制生物材料。
This study aimed at identifying putative modulations of tissue homeostatic parameters in corneal keratinocytes in response to biomechanical cues as basis for innovative cornea biomechanical-tailored biomaterials. Since cornea epithelial biomechanics is already described for contacts on nanostructures, we herein analyzed cell response to mechanical substrate elasticity. Therefore, corneal keratinocytes were established on physiologically-relevant elastic substrates of 40kPa, 130kPa but also on non-physiological stiff substrates of 1.74MPa for 3 days. qPCR revealed that changes in gene expression were only marginal between 40kPa and 130kPa, while significant modulations were seen on 1.74MPa substrates for most tissue-innate biomarkers under study. Gene expression fairly coincided with the protein, with differentiation progression biomarkers involucrin and fillagrin being already significantly increased between elasticities of 40kPa and 130kPa. Regarding focal adhesions, reinforcement was seen for ß1 integrin and phospho- p125FAKbetween 40kPa and 130kPa, while from 130kPa to 1.74MPa actin redistributed and phospho-p125FAKwas strikingly up-regulated. These findings suggest elasticity dependence for differentiation progression and focal adhesion dynamics of corneal keratinocytes, supporting the concept of biomechanics governed regulation of tissue homeostasis. Moreover, this concept in turn can be translated into prospective cornea-tailored biomaterials for therapeutic approaches in ophthalmology.