Quantitatively distinct requirements for signaling-competent cell spreading on engineered versus natural adhesion ligands.
Quantitatively distinct requirements for signaling-competent cell spreading on engineered versus natural adhesion ligands.
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信号传导细胞在工程粘附配体和天然粘附配体上传播的定量要求不同。
DOI：
10.1016/j.jconrel.2004.07.034
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Asthagiri,AnandR
中科院分区：
文献类型：
--
作者：
Richman,GabrielP;Tirrell,DavidA;Asthagiri,AnandR
To design synthetic microenvironments that elicit desired cell behaviors, we must better understand the molecular mechanisms by which cells interact with candidate biomaterials. Using cell lines with distinct α5β1integrin expression profiles, we demonstrate that this integrin mediates cell spreading on substrata coated with genetically engineered artificial extracellular matrix (aECM) proteins containing the RGD sequence (RGD-containing aECM protein [aRGD]) but lacking the PHSRN synergy site. Furthermore,aRGD-mediated adhesion stimulates an intracellular focal adhesion kinase (FAK) signal that is indicative of integrin tethering. Although bothaRGD and the natural ECM protein fibronectin (FN) support α5β1integrin-mediated cell spreading, quantitative single-cell analysis revealed thataRGD-mediated spreading requires ten-fold greater threshold amount of integrin expression than FN-mediated spreading. Our analysis demonstrates thataRGD-based substrata mediate both biophysical (cell spreading) and biochemical (FAK signaling) events via the α5β1integrin, albeit with efficacy quantitatively distinct from that of natural ECM proteins that possess the full spectrum of adhesion and synergy domains.
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发表时间：
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