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Using well-defined model surfaces to study cell adhesion.

机译：使用定义明确的模型表面研究细胞粘附。

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摘要

The work presented in this dissertation uses self-assembled monolayers as the platform for creating model substrates of the extracellular matrix in order to gain a clear picture of how cells attach and respond to their microenvironment. Two studies that took advantage of the control monolayer substrates have over ligand presentation are described, revealing important details about cell adhesion that more traditional substrates have been unable to provide. The first study addressed the synergistic versus competitive mechanisms of cell adhesion to monolayers presenting specific type III domains of the extracellular matrix protein fibronectin. This study confirmed that the RGD and PHSRN peptide ligands within fibronectin can independently and competitively mediate cell adhesion, although the PHSRN ligand is unable to sustain adequate cell spreading and signaling on its own. The second study focused on the integrin family of cell receptors and how the process of outside-in integrin activation can be influenced. This study utilized monolayer substrates presenting two different RGD ligands and revealed that increasing the binding affinity of the ligand alters the integrin equilibrium to favor more activated integrins. Overall, using self-assembled monolayers as model substrates in cell adhesion studies removes the ambiguities from which most other methods suffer due to their inability to present the extracellular matrix ligands in a well-controlled manner.
机译：本论文提出的工作以自组装单分子膜为平台，以创建细胞外基质的模型底物，以清晰了解细胞如何附着并响应其微环境。描述了两项利用对照单层底物优于配体表现的研究，揭示了更多传统底物无法提供的有关细胞粘附的重要细节。第一项研究探讨了细胞粘附至呈现细胞外基质蛋白纤连蛋白特定III型结构域的单层细胞的协同与竞争机制。这项研究证实，纤连蛋白内的RGD和PHSRN肽配体可以独立和竞争性地介导细胞黏附，尽管PHSRN配体无法独自维持足够的细胞扩散和信号传导。第二项研究的重点是细胞受体整联蛋白家族，以及如何影响由内而外的整联蛋白活化过程。这项研究利用了呈现两个不同RGD配体的单层底物，并揭示了增加配体的结合亲和力会改变整联蛋白平衡，从而有利于活化更多的整联蛋白。总的来说，在细胞粘附研究中使用自组装单层膜作为模型底物，消除了大多数其他方法由于无法以受控的方式呈现胞外基质配体而遭受的歧义。

著录项

  • 作者

    Eisenberg, Jessica Lynn.;

  • 作者单位

    The University of Chicago.;

  • 授予单位 The University of Chicago.;
  • 学科 Chemistry Biochemistry.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 156 p.
  • 总页数 156
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 宗教;
  • 关键词

  • 入库时间 2022-08-17 11:38:24

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