Multiscale Interaction of Pulmonary Gas Flow and Lung Tissue Mechanics

肺气流与肺组织力学的多尺度相互作用

• 批准号: 7758994
• 负责人: CHING-LONG LIN
• 金额: $ 36.66万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7758994
• 关键词: Abdomen; Adenosine; Adenosine Triphosphate; Adopted; Archives; Asthma; Automobile Driving; Bacteria; Biochemical; Biological; Biological Models; Biomedical Engineering; Breathing; Calcium Signaling; Calcium ion; Cell Culture Techniques; Cell model; Cells; Cellular biology; Characteristics; Chronic Obstructive Airway Disease; Clinical; Communities; Confocal Microscopy; Cyclic AMP; Cystic Fibrosis; Data; Databases; Daughter; Epithelial Cells; Failure; Funding; Gases; Generations; Grant; Heating; Height; Homeostasis; Human; Human Volunteers; Humidity; Image; In Vitro; Ions; Irritants; Link; Liquid substance; Lobe; Lung; Lung diseases; Maps; Measurement; Measures; Mechanics; Mediating; Medical Imaging; Metabolism; Modeling; Motion; Motivation; Mucociliary Clearance; Mucous body substance; Muscle Rigidity; Nucleotides; Organ; Particulate; Pathologic Processes; Pathway interactions; Physiological; Physiology; Process; Production; Public Health; Pulmonary Emphysema; Regulation; Research; Research Proposals; Resistance; Respiratory Diaphragm; Respiratory physiology; Role; Signal Transduction; Simulate; Smoker; Solid; Spottings; Stress; Structure; Structure of parenchyma of lung; Surface; System; Systems Biology; Techniques; Technology; Temperature; Testing; Thermodynamics; Tissues; Toxin; Translations; Trees; United States National Institutes of Health; Validation; Water; Work; X-Ray Computed Tomography; airway remodeling; base; detector; event cycle; experience; image registration; innovation; lung imaging; lung pressure; meetings; multidisciplinary; non-smoker; nucleotide metabolism; programs; public health relevance; receptor; repository; research study; response; rib bone structure; shear stress

DESCRIPTION (provided by applicant): The broad objective of this research is to apply the image-based fluid-structure interaction (FSI) technique to study the mechanical force resulting from the multiscale interactions between pulmonary gas flow and lung tissue mechanics, and its role in the distribution and progression of lung disease. A biological hypothesis motivating this work is that lung diseases alter mechanical force, which then alters stress-mediated adenosine triphosphate nucleotide release, disturbs periciliary liquid (PCL) water homeostasis, and weakens the integrated airway defense system, forming a vicious cycle of events. In a multidisciplinary effort, this proposal seeks to adopt an innovative systems biology approach that integrates mechanics and cell models to model transmittal of mechanical force from macro to micro scales, and further translation to biochemical responses at cellular level to maintain the PCL volume for mucociliary clearance. To achieve the objective and test the hypothesis, we propose the following specific aims. (1) Study the distributions of airflow-induced shear stress and airway-wall tissue stress in the central 6 generations of airways where the maximum resistance occurs. The emphasis will be placed on alteration of stresses due to airway rigidity, airway narrowing, and tissue stiffness, especially near the bifurcations in both upper and lower lobes as assessed in normal, asthmatic and emphysema subjects. (2) Study the biochemical responses of bronchial epithelial cells to the alteration of stresses in terms of the regional distributions of PCL water level and calcium ion concentration together with thermodynamics for heat and moisture in the human lung. The emphasis will be placed on deviation from PCL water homeostasis due to depletion or over-production of PCL volume near the bifurcations in both upper and lower lobes, and assess its implication on mucociliary transport. (3) Share the databases and models developed for this project with research and clinical communities via our medical image file archive system and model repository. To achieve these aims, we will extend our existing flow model to include lung tissue mechanics via image-registration-assisted FSI to simulate transmittal of mechanical force between airflow and tissue. We will also incorporate a stress-dependent nucleotide model into our existing model for calcium signaling and transmembrane ion and water fluxes in the ciliated epithelial cell. The fluid-structure (organ- tissue) mechanics model and the epithelial cell model will be integrated with regionally distributed airway thermodynamics to predict dynamic changes in the depth of the PCL layer and calcium ion concentration in the healthy and diseased airways. Both multi-detector row computed tomography (MDCT) experiments and cell culture experiments will be performed for model refinement and validation. PUBLIC HEALTH RELEVANCE: This proposal aims to adopt a systems biology approach that integrates mechanics and cell models to understand the interplay between mechanical forces and cellular biochemical responses for airway defense in the healthy and diseased lungs.

描述（由申请人提供）：本研究的主要目的是应用基于图像的流体-结构相互作用（FSI）技术研究肺气流和肺组织力学之间多尺度相互作用产生的机械力，及其在肺部疾病分布和进展中的作用。激发这项工作的生物学假设是，肺部疾病改变机械力，然后改变应激介导的三磷酸腺苷核苷酸释放，扰乱纤毛周围液体（PCL）水稳态，并削弱综合气道防御系统，形成恶性循环的事件。在一个多学科的努力，该提案旨在采用一种创新的系统生物学方法，集成力学和细胞模型，以模拟从宏观到微观尺度的机械力传输，并进一步翻译为细胞水平的生化反应，以保持PCL体积的粘膜纤毛清除。为了实现这一目标并检验假设，我们提出了以下具体目标。(1)研究气流诱导的切应力和气道壁组织应力在中央6代气道最大阻力发生处的分布。重点将放在由于气道刚度，气道狭窄，和组织硬度，特别是在正常，哮喘和肺气肿受试者的评估在上叶和下叶的分叉附近的应力的变化。(2)从人肺内PCL水位和钙离子浓度的区域分布以及热湿热力学角度研究支气管上皮细胞对应力变化的生化反应。重点将放在偏离PCL水稳态由于耗尽或过度生产的PCL量附近的分叉在上下叶，并评估其对粘液纤毛运输的影响。(3)通过我们的医学图像文件存档系统和模型库，与研究和临床社区共享为此项目开发的数据库和模型。为了实现这些目标，我们将扩展我们现有的流动模型，包括肺组织力学通过图像配准辅助FSI模拟气流和组织之间的机械力的传输。我们还将把一个应力依赖的核苷酸模型到我们现有的模型中的钙信号和跨膜离子和水通量的纤毛上皮细胞。流体-结构（器官-组织）力学模型和上皮细胞模型将与区域分布的气道热力学相结合，以预测健康和患病气道中PCL层深度和钙离子浓度的动态变化。将进行多探测器行计算机断层扫描（MDCT）实验和细胞培养实验，以进行模型优化和验证。 公共卫生相关性： 该提案旨在采用系统生物学方法，将力学和细胞模型相结合，以了解健康和患病肺部气道防御的机械力和细胞生化反应之间的相互作用。