Modeling of Endothelial Cell Adhesion Dynamics Modulated by Experimental Molecular Engineering

实验分子工程调节的内皮细胞粘附动力学建模

• 批准号: 0856333
• 负责人: Wing Liu
• 金额: $ 37.1万
• 依托单位: Northwestern University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-15 至 2012-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0856333&HistoricalAwards=false
• 关键词: Modeling; Endothelial; Cell; Adhesion; Dynamics

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).In experimental biomechanical studies, a common problem is the difficulty of conducting a large number of tests for the efficacy time course of engineering manipulation. An integrated experimental and computational molecular biomechanics model for the enhancement of endothelial cell adhesion in arterial reconstruction is proposed. Endothelial cells play a critical role for protecting blood vessels against thrombosis and atherosclerosis, which is associated with platelet activation and blood coagulation. Endothelial cell lining of arterial constructs is an effective approach for preventing intimal hyperplasia in reconstructed arteries. However, endothelial cells often detach from reconstructed arteries due to weak adhesion strength, hampering the effectiveness of endothelial cell lining. Hence, the research thrusts are: (1) the adhesion of endothelial cells will be enhanced by experimental molecular modulation of selected adhesion regulatory factors; (2) the focal contact association/dissociation rates of the intergrin receptor and ligand pair binding at the molecular level will be computed; and (3) the adhesion strength of modulated endothelial cells will be predicted by computational simulation under various hemodynamic conditions. Societal Impact and Intellectual Merit: Vascular thrombosis, intimal hyperplasia, and atherosclerosis are common disorders affecting about 50% of the human population. Thus, a novel investigation leading to a potential reduction in these disorders will elicit significant impact in the scientific as well as non-scientific communities. The proposed research, while using the arterial reconstruction model as an example, addresses a fundamental topic: enhancing a desired cell function by modulating molecular activities, a potentially effective engineering approach not only for basic scientific research but also for the treatment of pathological disorders. Although this investigation focuses on endothelial cell adhesion in arterial reconstruction, the concept of integrating computational approach with experimental molecular modulation of cell function can be generalized and used for other pathological disorders.

该奖项是根据2009年美国复苏和再投资法案(公法111-5)资助的。在实验生物力学研究中，一个常见的问题是难以对工程操作的功效时间过程进行大量测试。提出了动脉重建中内皮细胞黏附增强的实验和计算分子生物力学模型。内皮细胞在保护血管免受血栓形成和动脉粥样硬化的影响中起着至关重要的作用，而动脉粥样硬化和血栓形成与血小板活化和凝血有关。动脉结构内皮细胞衬里是预防重建动脉内膜增生的有效方法。然而，由于内皮细胞黏附强度较弱，血管内皮细胞经常脱离重建的动脉，阻碍了内皮细胞衬里的有效性。因此，研究的重点是：(1)通过对选定的黏附调节因子的实验分子调控来增强内皮细胞的黏附；(2)在分子水平上计算整合素受体和配体对结合的焦点接触结合/解离率；(3)通过计算模拟预测在不同血流动力学条件下调制后的内皮细胞的黏附强度。社会影响和智力价值：血管血栓形成、内膜增生和动脉粥样硬化是影响约50%人口的常见疾病。因此，一项导致这些疾病潜在减少的新研究将在科学界和非科学界产生重大影响。这项拟议的研究以动脉重建模型为例，解决了一个基本主题：通过调节分子活动来增强所需的细胞功能，这不仅对于基础科学研究，而且对于病理疾病的治疗，都是一种潜在有效的工程方法。虽然这项研究主要集中在动脉重建中的内皮细胞黏附，但将计算方法与实验分子调节细胞功能相结合的概念可以推广到其他病理疾病。