• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Rules of engagement enabling leukocyte rolling and adhesion: An in silico model study.
【24h】

Rules of engagement enabling leukocyte rolling and adhesion: An in silico model study.

机译：参与规则使白细胞滚动和粘附：计算机模型研究。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Rolling, activation, and adhesion on endothelial surfaces are necessary steps for the proper recruitment of leukocytes from circulating blood to sites of inflammation. Once at the target site, leukocytes help destroy pathogens and decompose damaged tissue. Inflammatory mechanisms, when uncontrolled, are also associated with diseases such as asthma, rheumatoid arthritis, and atherosclerosis. Improved therapeutics can be developed with a better understanding of the molecular-level events that mediate this process.This dissertation reports the development of a synthetic, in silico model for use as an experimental system for testing the plausibility of mechanistic hypotheses of how molecular components may interact to cause leukocyte behaviors during rolling, activation, and adhesion to endothelial surfaces. Object-oriented software components were designed, instantiated, verified, plugged together, and then operated in ways that can map concretely to mechanisms and processes believed responsible for leukocyte rolling, activation, and adhesion. The result is an in silico analogue of the wet-lab experimental systems to study leukocyte rolling and adhesion the experimentally measured phenotypic attributes of the analogue can be compared and contrasted to those of leukocytes from the referent systems.We first demonstrate that the in silico devices can generate behaviors similar to those observed in vitro at the cell-level and population-level, by comparing simulation results with data from three different in vitro experimental conditions. The validated model was then used to test the hypothesized mechanism of LFA-1 integrin clustering in adhesion. The in silico device showed that clustering was not necessary to achieve adhesion as long as densities of LFA-1 and its ligand ICAM-1 were above a critical level. Importantly, at low densities LFA-1 clustering enabled improved efficiency: adhesion exhibited measurable, cell level positive cooperativity.Our results provide convincing evidence for the feasibility of using synthetic in silico systems to improve our understanding of the molecular- and cellular-level events mediating leukocyte rolling, activation, and adhesion during inflammation. This work represents early, but important advances for future in silico research into plausible causal links between molecular-level events and the variety of systems-level behaviors that distinguish normal leukocyte adhesion from disease-associated adhesion.
机译：内皮表面的滚动，激活和粘附是白细胞从循环血液中正确募集到炎症部位的必要步骤。一旦到达目标部位，白细胞将帮助破坏病原体并分解受损的组织。当不受控制时，炎症机制也与诸如哮喘，类风湿性关节炎和动脉粥样硬化的疾病有关。可以更好地理解介导该过程的分子水平事件，从而开发出改良的治疗方法。本论文报告了合成的计算机模拟模型的开发，该模型可用作实验系统来检验分子组分如何可能的机制假设的合理性。相互作用在滚动，激活和粘附到内皮表面的过程中引起白细胞行为。面向对象的软件组件经过设计，实例化，验证，插入在一起，然后以可以具体映射到认为负责白细胞滚动，激活和粘附的机制和过程的方式进行操作。结果是湿实验室实验系统的计算机模拟，用于研究白细胞的滚动和粘附，可以将实验测量的类似物的表型属性与参照系统中的白细胞进行比较和对比。我们首先证明了计算机装置通过将模拟结果与来自三种不同体外实验条件的数据进行比较，可以产生与在细胞水平和种群水平上观察到的行为相似的行为。然后将验证的模型用于测试LFA-1整合素簇在粘附中的假设机制。硅计算机设备显示，只要LFA-1及其配体ICAM-1的密度高于临界水平，聚簇就不需要实现粘合。重要的是，在低密度的情况下，LFA-1聚类可提高效率：粘附力表现出可测量的细胞水平正协同性。我们的结果为使用合成计算机系统改善对分子和细胞水平事件介导的理解提供了令人信服的证据。炎症过程中白细胞滚动，激活和粘附。这项工作代表了未来的计算机科学研究的早期但重要的进展，这些研究涉及分子水平事件与各种系统水平行为之间的合理因果联系，以区分正常白细胞粘附与疾病相关粘附。

著录项

  • 作者

    Tang, Jonathan.;

  • 作者单位

    University of California, Berkeley.;

  • 授予单位 University of California, Berkeley.;
  • 学科 Engineering Biomedical.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 109 p.
  • 总页数 109
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号