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)：了解、操纵和控制细胞黏附过程对于制定战略至关重要，其中包括通过循环系统靶向药物输送、在生物反应器中生长自组装组织结构以及用于检测环境细菌的微型生物传感器。然而，我们对流体剪切流动条件下细胞-细胞黏附的了解中的关键问题仍然没有解决。因此，申请者正在开发一种基于浸没边界方法的计算模型，以模拟细胞与细胞之间的相互作用，该模型既考虑了分子相互作用，也考虑了细胞膜对整体流动的响应。拟议的数值工具的构建和开发将通过测量剪切条件下受体介导的白细胞-金黄色葡萄球菌细菌细胞相互作用来指导和验证，这对免疫反应至关重要。金黄色葡萄球菌可引起感染，导致严重后果，包括败血症合并多器官衰竭、心内膜炎、关节炎、脊椎骨髓炎、硬膜外脓肿和眼内炎。我们的剪切流中细胞的计算模型被用来模拟可变形细胞之间的细胞间碰撞。此外，通过将可变形细胞模型与受体-配体结合的概率模型相结合，得到了白细胞S的重要生物力学和动力学参数。可以计算金色粘附剂的相互作用。结合真实的细胞细节将使我们能够更好地估计模型参数，如细胞间接触面积、接触时间以及作为影响细胞黏附的细胞属性和流体动力剪切的函数的压缩和拉力。这些研究还将为分析其他受体介导的细胞相互作用提供一个框架，这些相互作用在生物技术和细胞生理学的不同过程中发挥着重要作用，并将极大地促进我们在流体物理、血管生物学和纳米级分子相互作用界面上的理解。