The Virtual Lung Project: Integrated Modeling of Epithelial Fluid Flows

虚拟肺项目：上皮液流的集成建模

• 批准号: 7259472
• 负责人: RICHARD SUPERFINE
• 金额: $ 70.61万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7259472
• 关键词: Address; Astronomy; Biochemical; Biochemistry; Biological; Biophysics; Chemistry; Cilia; Class; Complex; Computer Simulation; Condition; Cultured Cells; Cystic Fibrosis; Development; Environment; Epithelial; Epithelial Cells; Exclusion; Failure; Feedback; Friction; Gene Mutation; Glycoproteins; Goals; Guns; Health; Human; Infection; Ions; Liquid substance; Lubrication; Lung; Mathematics; Measures; Membrane; Modeling; Molecular; Mucins; Mucous body substance; Nucleosides; Nucleotides; Physics; Physiology; Polymers; Principal Investigator; Production; Property; Proteins; Range; Regulation; Research; Research Personnel; Rheology; Science; Series; Signaling Molecule; Stress; Structure; Structure of parenchyma of lung; Surface; System; Techniques; Therapeutic; Time; Virus; Water; airway surface liquid; base; cellular microvillus; crosslink; extracellular; fluid flow; gastrointestinal microvillus; millimeter; molecular modeling; molecular scale; particle; programs; research study; response; sensor; shear stress; simulation; theories; therapy design; virtual; viscoelasticity

DESCRIPTION (provided by applicant): The flow of liquid on mucosal surfaces is ubiquitous in human physiology. The failure of cilia and airflow induced liquid flow in the lungs (mucus clearance), as in Cystic Fibrosis, primary cilia dyskinesis, and environmentally damaged lungs, leads to severe health problems as the lung tissue will be destroyed by infections that cannot be cleared. Significant progress has been made in recent years in identifying the key genetic mutation responsible for Cystic Fibrosis, studying the hydrodynamics and biochemistry of airway mucus and beginning to develop effective treatments. In parallel, theory and simulation have begun to tackle issues such as the basis for force production in biological molecules, the rheology of biological fluids and hydrodynamics of viscous, complex flows. We stand at a critical time when an understanding of biological systems assembled into a unified simulation is essential for making breakthroughs in the science of microbiological hydrodynamics. The approach of this project is to develop sophisticated physics-based models of polymer dynamics and viscoelastic hydrodynamics in close coordination with experiments in human bronchial epithelial cell cultures. Through a combination of established and advanced techniques, the project will develop an integrated view of the biophysics of the mucus clearance system from the molecular scale seen by signaling molecules and viruses, up to the millimeter scales that control flow. By combining a team of researchers from Applied Mathematics, Chemistry, Physics and Astronomy, Biochemistry and Biophysics, and the Cystic Fibrosis Center, the long term goal is to develop an integrated computational model that will be able to predict and evaluate truly effective therapeutic strategies. The challenge in developing this comprehensive approach is to proceed through a series of research goals that accomplish short range impact.

描述（由申请人提供）：粘膜表面上的液体流动在人体生理学中普遍存在。纤毛和气流引起的肺中液体流动（粘液清除）的失败，如在囊性纤维化、原发性纤毛运动障碍和环境损伤的肺中，导致严重的健康问题，因为肺组织将被无法清除的感染破坏。近年来，在确定囊性纤维化的关键基因突变，研究气道粘液的流体动力学和生物化学以及开始开发有效的治疗方法方面取得了重大进展。与此同时，理论和模拟已经开始解决诸如生物分子中力产生的基础、生物流体的流变学和粘性复杂流动的流体动力学等问题。我们站在一个关键时刻，当生物系统的理解组装成一个统一的模拟是必不可少的微生物流体动力学科学的突破。该项目的方法是开发复杂的基于物理学的聚合物动力学和粘弹性流体力学模型，并与人类支气管上皮细胞培养实验密切配合。通过现有技术和先进技术的结合，该项目将开发粘液清除系统的生物物理学的综合视图，从信号分子和病毒看到的分子尺度到控制流量的毫米尺度。通过将来自应用数学，化学，物理学和天文学，生物化学和生物物理学以及囊性纤维化中心的研究人员团队结合起来，长期目标是开发一个集成的计算模型，该模型将能够预测和评估真正有效的治疗策略。发展这种综合方法的挑战是通过一系列实现短期影响的研究目标。