Collaborative Research: Interactions of Airborne Engineered Nanoparticles with Lung Surfactant Films

合作研究：空气传播的工程纳米粒子与肺表面活性剂膜的相互作用

• 批准号: 2040301
• 负责人: Younjin Min
• 金额: $ 36.52万
• 依托单位: University of California-Riverside
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2040301&HistoricalAwards=false
• 关键词: Collaborative; Research; Interactions; Airborne; Engineered

Rapid developments in nanotechnology have led to the production and use of various types of engineered nanoparticles. It is inevitable that airborne nanoparticles may be released to the environment and may cause potential consequences for human health, in particular, in the respiratory tract including the lung (alveolar region) once inhaled. The lung surfactant, which covers the alveoli as a thin liquid film, represents the first line of defense against such airborne nanoparticles at the air-liquid interface. This collaborative project, involving a synergistic combination of experimental and computational studies, seeks to study the effects of physicochemical and structural properties of engineered nanoparticles on interfacial flow behaviors and stability of surfactant films. This research activity also is aimed at obtaining a better fundamental understanding of the molecular interactions arising between surfactant films and potentially hazardous engineered nanoparticles in realistically imitated physiological conditions. Fundamental knowledge gained through this project is, therefore, expected to provide new insights into the subsequent retention, translocation, and clearance of inhaled nanoparticles and the sequential processes associated with engineered nanoparticle toxicity overall. The project results will also advance the basic knowledge of the fate of biological nanoparticles, such as coronavirus virions, in the lungs that may have practical implications in medicine. Educational and mentoring aspects of this project include training graduate students in advanced surface science tools and computational techniques, mentoring underrepresented undergraduate students in research, and developing teaching modules and subjects relevant to nanoparticle interactions in biological systems. As the production and use of engineered nanoparticles increases day by day, it is inevitable that these nanoparticles will be released to the environment. Therefore, the occurrence and fate of engineered nanoparticles in the environment, and the potential consequences on human health have been increasingly recognized as issues of critical importance. In particular, airborne nanoparticles can result in a much greater likelihood and extent of exposure to the environment and thus living beings. This collaborative project will focus on improving our fundamental understanding of the molecular interactions between engineered nanoparticles and lung surfactant films at multiple-length scales. The project will evaluate the distribution and fate of inhaled airborne nanoparticles in the respiratory tract. This research project is structured around two specific objectives. First, this project aims to determine the effects of physicochemical and structural properties of inhaled engineered nanoparticles on the viscoelastic responses and interfacial stability of lung surfactant films. Second, the project will generate fundamental data concerning the molecular mechanisms of interfacial interactions in lung surfactant monolayers and multilayers in the absence and presence of engineered nanoparticles at multiple length scales in physiological environments. To achieve these goals, a synergistic combination between experimental and computational approaches will be employed. Experimental advances include a specially modified Langmuir trough, a quartz crystal microbalance with dissipation coupled with a custom-made particle generator unit, and a highly sophisticated surface forces apparatus. The computational component is based on a new coarse-grained computational framework for investigations of nanoscale interfacial processes at air-liquid interfaces, including dissipative particle dynamics models to predict the composition dependent surface tension, elasticity, viscosity, and stability of lung surfactant monolayer and bilayers with doped engineered nanoparticles. These collaborative experimental and computational studies of nanoscale interfacial phenomena are expected to provide qualitative and quantitative information on the viscoelastic properties of lung surfactant films and the attendant response to shear stresses upon breathing affected by adhered/piercing engineered nanoparticles. In addition, the principal investigators will generate systematic information on molecular interactions of engineered nanoparticles with the lung surfactant system, especially in terms of adhesion and fusion behaviors that are related to the structural integrity of lung surfactant films. The findings gained through this project will improve mechanistic understanding of the adhesion and translocation of nanoparticulate matter (e.g., coronavirus virions) across other general cell membranes. Educational components of this project involve training graduate students and mentoring undergraduate students from underrepresented groups in engineering through various programs offered at Rutgers University and the University of California, Riverside.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

纳米技术的快速发展导致了各种类型的工程纳米颗粒的生产和使用。不可避免的是，空气传播的纳米颗粒可能被释放到环境中，并且可能对人类健康造成潜在的后果，特别是在呼吸道中，包括一旦被吸入的肺（肺泡区域）。肺表面活性剂以薄液膜形式覆盖肺泡，是对抗气液界面上此类空气传播纳米颗粒的第一道防线。该合作项目涉及实验和计算研究的协同结合，旨在研究工程纳米粒子的物理化学和结构特性对界面流动行为和表面活性剂膜稳定性的影响。这项研究活动也旨在获得更好的基本了解表面活性剂膜和潜在危险的工程纳米粒子在现实模拟的生理条件之间产生的分子相互作用。因此，通过该项目获得的基础知识有望为吸入纳米颗粒的后续保留、易位和清除以及与工程化纳米颗粒毒性相关的整体顺序过程提供新的见解。该项目的结果还将推进生物纳米粒子（如冠状病毒粒子）在肺部的命运的基本知识，这可能对医学产生实际影响。该项目的教育和指导方面包括在先进的表面科学工具和计算技术方面培训研究生，指导研究中代表性不足的本科生，以及开发与生物系统中纳米粒子相互作用相关的教学模块和科目。随着工程纳米颗粒的生产和使用日益增加，这些纳米颗粒将不可避免地释放到环境中。因此，工程纳米粒子在环境中的发生和归宿，以及对人类健康的潜在影响已越来越被认为是至关重要的问题。特别是，空气中的纳米颗粒可能会导致更大的可能性和程度暴露于环境和生物。这个合作项目将专注于提高我们对工程纳米颗粒和肺表面活性剂膜在多个长度尺度上分子相互作用的基本理解。该项目将评估吸入的空气中纳米颗粒在呼吸道中的分布和结局。本研究项目围绕两个具体目标展开。首先，本项目旨在确定吸入工程纳米粒子的物理化学和结构特性对肺表面活性物质膜的粘弹性反应和界面稳定性的影响。第二，该项目将产生有关肺表面活性剂单层和多层界面相互作用的分子机制的基础数据，在生理环境中，在多个长度尺度上存在和不存在工程纳米颗粒。为了实现这些目标，将采用实验和计算方法之间的协同组合。实验进展包括一个特别修改的朗缪尔槽，石英晶体微量天平与耗散耦合定制的粒子发生器单元，和一个高度复杂的表面力装置。计算组件是基于一个新的粗粒度的计算框架的纳米级的界面过程的调查，在空气-液体界面，包括耗散粒子动力学模型来预测组合物依赖的表面张力，弹性，粘度和稳定性的肺表面活性剂单层和双层掺杂工程纳米粒子。这些纳米级界面现象的合作实验和计算研究，预计将提供定性和定量的信息肺表面活性剂膜的粘弹性和随之而来的响应剪切应力呼吸时受粘附/穿刺工程纳米粒子的影响。此外，主要研究者将生成关于工程纳米颗粒与肺表面活性剂系统的分子相互作用的系统信息，特别是在与肺表面活性剂膜的结构完整性相关的粘附和融合行为方面。通过该项目获得的发现将提高对纳米颗粒物质的粘附和移位的机械理解（例如，冠状病毒体）穿过其他一般细胞膜。该项目的教育部分包括通过罗格斯大学和滨江的加州大学提供的各种项目，培训研究生和指导来自工程领域代表性不足群体的本科生。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。