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Temporal differences in Erk1/2 activity distinguish among combinations of extracellular matrix components.

机译:Erk1 / 2活性的时间差异区分细胞外基质成分的组合。

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Rational design of biomaterials requires understanding how cells interrogate their microenvironment. In this study, human umbilical vein endothelial cells are cultured on combinations of extracellular matrix (ECM) components (collagen I, collagen IV, vitronectin, fibronectin, laminin, heparan sulfate proteoglycan, chondroitin sulfate proteoglycan), and the phosphorylation of four intracellular signaling kinases (Erk1/2, JNK, Akt1, and NFkappaB) is quantified. These combinations of ECM components elicit different temporal patterns of Erk1/2 phosphorylation. Collagen I-containing substrates cause Erk1/2 phosphorylation to reach maximal levels at 30 min and remain near maximal levels until 90 min. Collagen IV/laminin substrates elicit maximal phosphorylation at 30-45 min, and then phosphorylation decreases substantially at 60-90 min. All other combinations studied (collagen IV and vitronectin-based combinations) cause an increase in phosphorylation at 30-45 min, but not to maximal levels; maximal phosphorylation is reached by 60-90 min. These temporal patterns of phosphorylation may explain how a limited number of intracellular signaling pathways can distinguish among thousands of possible combinations of microenvironmental cues by adding to the information contained in each cell signaling pathway.
机译:合理设计生物材料需要了解细胞如何干扰其微环境。在这项研究中,人脐静脉内皮细胞在细胞外基质(ECM)成分(胶原蛋白I,胶原蛋白IV,玻连蛋白,纤连蛋白,层粘连蛋白,硫酸乙酰肝素蛋白聚糖,软骨素硫酸盐蛋白聚糖)的组合以及四种细胞内信号激酶的磷酸化条件下培养(Erk1 / 2,JNK,Akt1和NFkappaB)被量化。 ECM组件的这些组合会引发Erk1 / 2磷酸化的不同时间模式。含胶原蛋白I的底物会导致Erk1 / 2磷酸化在30分钟时达到最高水平,并保持接近最高水平,直至90分钟。胶原IV /层粘连蛋白底物在30-45分钟时引起最大磷酸化,然后在60-90分钟时磷酸化显着降低。研究的所有其他组合(胶原蛋白IV和基于玻连蛋白的组合)在30-45分钟时引起磷酸化增加,但未达到最大水平。 60-90分钟达到最大磷酸化。这些磷酸化的时间模式可以解释有限数量的细胞内信号传导途径如何通过添加到每个细胞信号传导途径所包含的信息中来区分数千种可能的微环境线索。

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