Collaborative Research: Effects of interfacial viscosities on flow of lung surfactants

Hirsa，Amir H.CBET-1064644Broader的影响和背景：正常肺的液体衬里被表面活性剂覆盖。液体衬里对于氧气摄取和二氧化碳排放是必不可少的，然而，如果没有这些被称为表面活性剂的表面张力降低材料，呼吸将是困难的，如果不是不可能的话。除了降低表面张力以最大限度地减少呼吸做功外，肺表面活性物质还会改变呼吸周期中的表面张力，以保护肺泡免受呼气时的塌陷和吸气时的过度膨胀。功能表面活性物质的缺乏会导致呼吸窘迫综合征，这对成年人和早产儿都是一种潜在的致命疾病。肺表面活性物质替代疗法已经在降低早产儿死亡率方面取得了重大进展，但进一步的改善可以受益于对相关界面流体动力学的更好了解。目前的肺表面活性物质流体动力学模型忽略了表面粘度，这可能对肺表面活性物质流体动力学有重要贡献。有必要了解表面粘度在肺表面活性物质中的作用，因为在小尺度上，例如肺泡内液体的作用，表面粘度的相对影响与表面张力的相对影响相当。将研究降低肺部液体衬里表面张力的天然和人造材料的运动。利用先进的计算机模型和最新发展的实验技术，将研究肺表面活性物质的主要成分DPPC(二棕榈酰磷脂酰胆碱)的行为。将详细研究最近发现的DPPC覆盖液层的各种流动特性。拟议的项目与以前的研究不同之处在于，它弥合了两个极端之间的巨大分歧：(I)纯理论方法，假设没有与肺表面活性物质相关的固有界面粘度；(Ii)纯经验方法，使用特别方程解释实验观察到的肺表面活性物质的反应。目前，绝大多数肺表面活性物质研究分为这两个阵营中的一个或另一个。前者缺乏解释真实肺表面活性物质行为的许多方面的能力，而后者缺乏预测给定的表面活性物质将如何响应不同流动条件的能力。在模型表面活性物质体系(如DPPC)中界面粘度的测量和建模的改进可能有助于人们更好地了解天然肺表面活性物质的功能。所开发的功能随后可用于多组分肺表面活性物质系统。最终，该项目的结果可能有助于加快开发更有效的治疗方法。多学科团队(来自机械工程和数学)，凭借其卓有成效的协作记录，将提供一个极好的机会来教育研究生和本科生界面流体力学。该项目将开发一种结合实验和计算的协同能力，以解释与DPPC相关的领先阶界面粘弹性流体力学，描绘其各种流动状态。到目前为止，磷脂DPPC是肺表面活性物质中最常见的成分，占肺表面活性物质质量的55%。这种高度两亲性的分子有一个亲水的极头和一对疏水的尾巴，这使得它基本上不溶于水。它的平衡界面性质将被测量并纳入到考虑表面变形、界面加速和时空表面活性剂浓度的预测模型中。该模型将直接针对界面面积随时间变化较大的正则流进行实验测试，然后用于预测尺度太小而无法进行实验测量的动力学。这将有助于更好地理解和模拟界面的内在性质，包括表面张力梯度、表面剪切和膨胀粘度所产生的弹性效应，以及界面和整体流动之间的粘性耦合。

Hirsa, Amir H.CBET-1064644Broader Impact and Background: The liquid lining of normal lungs is covered by surfactants. The liquid lining is essential for oxygen intake and carbon dioxide output, however without these surface-tension-reducing materials, known as surfactants, breathing would be laborious if not impossible. Aside from reducing the surface tension to minimize the work of breathing, lung surfactants also vary the surface tensionduring the breathing cycle in order to protect the alveoli against collapse on exhalation and over-expansion upon inhalation. A lack of functioning surfactants leads to respiratory distress syndrome, a potentially fatal condition in both adults and premature infants. Replacement lung surfactant therapy has already made major inroads in reducing the mortality rate amongst pre-term infants, but further improve-ments can benefit from a better understanding of the associated interfacial hydrodynamics. Present models of lung surfactant hydrodynamics neglect surface viscosities, which may make a significant contribution. There is a need to understand the role of surface viscosities in lung surfactants because at small scales, such as those of the liquid lining the alveoli, the relative effects of surface viscosities are comparable to that of surface tension. The movement of natural and artificial materials that reduce the surface tension of the liquid lining of lungs will be studied. Using advanced computer models and recently developed experimental techniques, the behavior of DPPC (dipalmitoyl phosphatidylcholine), the primary constituent of lung surfactant, will be examined. Various flow characteristics of DPPC-covered liquid layers, that have recently been revealed, will be examined in detail. The proposed project differs from previous studies in that it bridges the vast divide between the two extremes of (i) purely theoretical approaches that assume no intrinsic interfacial viscosities associated with lung surfactants and (ii) purely empirical approaches that use ad hoc equations to explain experimentally observed responses of lung surfactants. Presently, the vast majority of lung surfactant research falls into one or the other of these two camps. The former lack the ability to explain many aspects of how real lung surfactants behave and the latter lack the ability to predict how a given surfactant will respond to a different set of flow conditions.Improvements in measurement and modeling of interfacial viscosities in model surfactant systems, such as DPPC, may help one to understand better the functioning of natural lung surfactants. The capabilities developed can be subsequently used for multi-component lung surfactant systems. Ultimately, the results of this project may help speed up the development of more effective therapies. The multidisciplinary team (from mechanical engineering and mathematics), with its proven track record of productive collaboration, will provide an excellent opportunity to educate graduate and undergraduate students in interfacial hydrodynamics.Intellectual Merit. The project will develop a synergistic capability incorporating experiments and computations to account for the leading order interfacial viscoelastic hydrodynamics associated with DPPC, delineating its various flow regimes. By far, the phospholipid DPPC is the most prevalent component of lung surfactants, constituting 55{60% of lung surfactant by mass. This highly amphiphilic molecule has a hydrophilic polar head and twin hydrophobic tails, making it essentially insoluble in water. Its equilibrium interfacial properties will be measured and incorporated into a predictive model taking into account surface deformation, interfacial acceleration and spatio-temporal surface sur-factant concentration. The model will be tested directly against experiments for a canonical flow with large time-dependent changes in the interfacial area, and then used to predict the dynamics at scales too small for experimental measurements. This will provide a much-needed improved understanding and modeling of the intrinsic interfacial properties, including the elastic effects due to surface tension gradients, surface shear and dilatational viscosities, and the viscous coupling between the interfacial and bulk flows.