Computational model of cellular adhesion in bulk flows

散装流中细胞粘附的计算模型

• 批准号: 7017762
• 负责人: CHARLES Dionisio EGGLETON
• 金额: $ 31.41万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE COUNTY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-15 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7017762
• 关键词: Staphylococcus aureus; bacteria infection mechanism; binding sites; cell adhesion; cell cell interaction; clinical research; computer simulation; electrocardiography; fluid flow; hemodynamics; host organism interaction; human subject; immune response; leukocytes; ligands; mathematical model; model design /development; polymerase chain reaction; receptor binding; shear stress

DESCRIPTION (provided by applicant): Understanding, manipulating and controlling cellular adhesion processes is crucial to developing strategies among others, to target drug delivery via the circulatory system, grow self-assembling tissue structures in bioreactors, and miniaturize biosensors for the detection of environmental bacteria. Yet, key issues in our knowledge of cell-cell adhesion under hydrodynamic shear flow conditions remain unresolved. Therefore a computational model based on the immersed boundary method is being developed by the applicants to simulate cell-cell interactions that accounts for both the molecular interactions and the response of the cell membrane to the bulk flow. The proposed construction and development of the numerical tools will be guided and validated by measurements of receptor-mediated leukocyte-Staphylococcus Aureus bacterial cell interactions under shear conditions, critical to the immune response. Staphylococcus Aureus bacterial strains are responsible for infections which may lead to devastating consequences including sepsis with multi-organ failure, endocarditis, arthritis, vertebral osteomyelitis, epidural abscess and endophthalmitis. Our computational model of a cell in a shear flow is used to simulate intercellular collisions between deformable cells. Moreover, by integrating the deformable cell model with a probablistic model of receptor-ligand binding, important biomechanical and kinetic parameters for leukocyte-S. Aureus adhesive interactions can be calculated. Incorporating realistic cellular details will enable us to better estimate the model parameters such as intercellular contact area, contact duration and compressive and tensile forces as a function of the cellular properties and hydrodynamic shear that influence cellular adhesion. The proposed studies will also provide a framework for analyzing other receptor-mediated cellular interactions that play a fundamental role n diverse processes in biotechnology and cell physiology, and will significantly advance our understanding at the interface of fluid physics, vascular biology and nano-scale molecular interactions.

描述（由申请人提供）：理解，操纵和控制细胞粘附过程对于制定策略以及其他策略至关重要，可以通过循环系统靶向药物递送，在生物反应器中生长自组装的组织结构，并使生物传感器微型生物传感器以检测环境细菌。然而，在流体动力剪切流条件下我们对细胞细胞粘附的了解中的关键问题仍未解决。因此，申请人正在开发基于沉浸式边界方法的计算模型，以模拟细胞 - 细胞相互作用，以解释分子相互作用和细胞膜对散装流量的响应。通过测量受体介导的白细胞螺旋杆菌金黄色可球菌细菌细胞相互作用在剪切条件下，对数值工具的构建和开发将得到指导和验证，这对免疫反应至关重要。金黄色葡萄球菌细菌菌株是导致可能导致毁灭性后果的感染，包括败血症，具有多器官衰竭，心内膜炎，关节炎，椎骨骨髓炎，硬膜外脓肿和内po虫。我们的剪切流中细胞的计算模型用于模拟可变形细胞之间的细胞间碰撞。此外，通过将可变形的细胞模型与白细胞-S受体配体结合，重要生物力学和动力学参数的概率模型整合在一起。可以计算金黄色粘合剂相互作用。结合现实的细胞细节将使我们能够更好地估计模型参数，例如细胞间接触区域，接触持续时间以及压缩力和拉伸力，这是细胞特性的函数以及影响细胞粘附的流体动力剪切。拟议的研究还将提供一个框架，用于分析其他受体介导的细胞相互作用，这些相互作用在生物技术和细胞生理学中发挥了基本作用，并将大大提高我们对流体物理学，血管生物学和纳米尺度分子相互作用的界面的理解。