Transport of Virus-like Nanoparticles through Mucus

Covid-19是由严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）引起的疾病。与许多其他病毒类似，这种病毒的形状接近球形，其核心是蛋白质-核酸复合物，周围是由蛋白质修饰的脂质双分子层包裹的包膜。病毒降落在呼吸道表面后，需要通过密集、粘稠和不均匀的粘液网络，在不断拍打的纤毛下，试图清除被困的病毒。这个实验项目将使用柔软的片状纳米粒子作为病毒粒子，凝胶形成的粘蛋白分子作为粘液屏障，剪切流作为纤毛的跳动。该模型系统将捕获相关的基础物理并生成可重复的结果，这些结果将揭示颗粒的柔软度、颗粒与模型粘液分子的相互作用以及模型粘液分子网络状态的波动如何影响黏液层之间的运输。这项研究将使人们更好地了解空气传播的病毒是如何与粘膜相互作用的，这将有助于对抗疾病。研究生和本科生将接受跨学科领域的培训，这将为他们探索广泛的职业机会做好准备。初高中学生将被训练参加STEM竞赛，研究团队将担任科学奥林匹克竞赛的教练。该项目的目的是研究软片状纳米颗粒（NPs）通过粘蛋白凝胶和恒定滑动速度的溶液的运输行为。核（金）-（凝胶）壳NPs的直径为50nm至150nm，弹性模量为0.1 kPa至10kpa，表面用胺、羧酸和聚乙二醇功能化。纤毛的同步跳动将通过应用生理学相关频率从2hz到20hz的三角剪切波来模拟。实验将利用波动相关光谱（FCS）在动态范围内测量40年来均方位移的时间依赖性。FCS测量的亚微米尺度的扩散将通过毛细管渗透实验与生理相关的较厚黏液层的传输进行比较。相位调制椭偏、流变学和动态光散射实验将进行量化粒子-基质相互作用、网络的粘弹性及其波动。该研究将解决纳米级动力学如何与黏液的结构、流变学和屏障特性耦合的基本问题。从更广泛的角度来看，所获得的知识将有助于更好地理解拥挤的生物系统（如细胞质、微生物生物膜和细胞外基质）以及各种工程流体（包括凝胶、乳液和堵塞系统）中颗粒和大分子的运输。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Covid-19 is the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus, similar to many others, is nearly spherical in shape with a core of protein-nucleic acid complex surrounded by an envelope of a protein-decorated lipid bilayer. After landing on the respiratory tract surface, viruses need to navigate through a dense, viscous, and heterogeneous mucus network, which is under constant beating of cilia that try to clear the trapped virus away. This experimental project will use soft, patchy nanoparticles as virions, gel-forming mucin molecules as the mucus barrier, and a shear flow as the beating of cilia. The model system will capture the pertinent underlying physics and generate reproducible results that will reveal how transport across mucus layers is affected by the softness of the particles, particle interactions with the model mucus molecules and fluctuations in the state of the model mucus molecular network. The research will lead to a better understanding of how air-borne viruses interact with the mucus membrane, which will help fight against diseases. Graduate and undergraduate students will be trained in an interdisciplinary field that will prepare them to explore a wide range of career opportunities. Middle and high school students will be trained to participate in STEM competitions with the research team serving as a coach for the Science Olympiad Tournaments. The objective of the project is to investigate the transport behavior of soft patchy nanoparticles (NPs) through mucin gels and solutions subjected to constant sliding velocity. Core(gold)-(gel)shell NPs will be used with diameters from 50 nm to 150 nm, elastic moduli from 0.1 kPa to 10 kPa, and surfaces functionalized with amine, carboxylic acid, and poly(ethylene glycol). The synchronized beating of cilia will be mimicked by applying a triangular shear wave of physiologically relevant frequencies from 2 Hz to 20 Hz. The experiments will measure the time-dependence of mean-square-displacement over four decades in dynamic range by using fluctuation correlation spectroscopy (FCS). Diffusion at sub-micrometer length scale as measured by FCS will be compared with transport through physiologically relevant thicker mucus layer by a capillary penetration experiment. Phase modulated ellipsometry, rheology, and dynamic light scattering experiments will be performed to quantify the particle-matrix interaction, viscoelasticity of the network, and its fluctuation. The research will address the fundamental question of how the nano-scale dynamics couples with the structure, rheology, and barrier property of mucus. From a broader perspective, the knowledge gained will be relevant to better understand the transport of particles and macromolecules in crowded biological systems, such as cytoplasm, microbial biofilms, and extracellular matrix, as well as in various engineering fluids, including gels, emulsions, and jammed systems.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.