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Ligand Anchorage and Materials Stiffness to Modulate Cell Adhesion Signals

配体锚定和材料刚度调节细胞粘附信号

基本信息

批准号：
180041759
负责人：
Professor Dr. Tilo Pompe
金额：
--
依托单位：
Arbeitsgruppe Biophysikalische Chemie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2010
资助国家：
德国
起止时间：
2009-12-31 至 2013-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/180041759?language=en
关键词：
Ligand Anchorage Materials Stiffness Modulate

项目摘要

Physicochemical Coes of the extracellular microenvironment aect fate decisions of living cells. We aim to modulate ligand anchorage to materials surfaces in order to dissect the highly convoluted signalling pathways of major exogenous cues in cell adhesion. Thereby we want to demonstrate the specic impact of ligand anchorage in relation to two other important cues, namely materials stiffness and ligand density in a multiparameter approach independently of each other. Ligand anchorage will be modulated from strong covalent coupling to gradually weaker non-covalent intermolecular interactions of cell adhesion ligands like fibronectin to the topmost surface of the polyacrylamide hydrogel layers as it allows to tune receptor forces of adherent cells. Ligand density is adjusted during ligand coupling to the hydrogel layers, while hydrogel stiffness can be controlled via its cross-linking density. Using such a materials platform the magnitude and time dependence of the biophysical cell response will be assessed in terms of traction force cytometry. The biophysical characterisation will be accompanied by biochemical quantification of intracellular signals, such as protein expression and phosphorylation state. The correlation of both the dissected biophysical and biochemical cell response to each other is expected to provide new insights in cell adhesion signalling and the specific impact of ligand anchorage. The results are envisioned to enable a targeted materials design of cell culture scaffolds for tissue engineering and regenerative therapies.

细胞外微环境的物理化学核心影响着活细胞的命运决定。我们的目标是调节配体锚定到材料表面，以剖析细胞粘附中主要外源线索的高度复杂的信号通路。因此，我们希望以相互独立的多参数方法证明配体锚定与其他两个重要线索（即材料刚度和配体密度）相关的特定影响。配体锚定将被调节从强共价偶联到逐渐减弱的非共价分子间相互作用的细胞粘附配体，如纤维连接蛋白到聚丙烯酰胺水凝胶层的最上层，因为它允许调节粘附细胞的受体力。配体密度在配体与水凝胶层的耦合过程中进行调节，而水凝胶的刚度可以通过其交联密度来控制。使用这样的材料平台，生物物理细胞反应的幅度和时间依赖性将根据牵引力细胞术进行评估。生物物理表征将伴随着细胞内信号的生化量化，如蛋白质表达和磷酸化状态。解剖的生物物理和生化细胞对彼此的反应的相关性有望为细胞粘附信号传导和配体锚定的特定影响提供新的见解。这些结果有望为组织工程和再生治疗提供细胞培养支架的靶向材料设计。