The Virtual Lung Project: Integrated Modeling of Epithelial Fluid Flows

描述(申请人提供)：液体在粘膜表面的流动在人体生理学中普遍存在。纤毛和气流导致肺部液体流动的失败(粘液清除)，如囊性纤维化、原发纤毛运动障碍和环境破坏的肺，会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，在确定导致囊性纤维化的关键基因突变、研究呼吸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。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。我们正处在一个关键时刻，将对生物系统的理解整合到一个统一的模拟中，对于在微生物流体动力学科学中取得突破是至关重要的。该项目的方法是开发复杂的基于物理的聚合物动力学和粘弹性流体动力学模型，并与人支气管上皮细胞培养实验密切配合。通过结合成熟和先进的技术，该项目将从信号分子和病毒看到的分子尺度，到控制流动的毫米尺度，开发粘液清除系统的生物物理学的综合视图。通过将来自应用数学、化学、物理和天文学、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能够预测和评估真正有效的治疗策略的集成计算模型。开发这一综合方法的挑战是通过一系列研究目标来实现短期影响。

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.