Transport of Virus-like Nanoparticles through Mucus

COVID-19是由严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）引起的疾病。这种病毒与许多其他病毒相似，形状接近球形，具有蛋白质-核酸复合物的核心，被蛋白质修饰的脂质双层的包膜包围。在降落在呼吸道表面后，病毒需要通过一个密集，粘稠和异质的粘液网络，这是在纤毛的不断跳动下，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学并生成可再现的结果，这些结果将揭示跨粘液层的运输如何受到颗粒的柔软度、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的影响。这项研究将有助于更好地了解空气传播的病毒如何与粘膜相互作用，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，为他们探索广泛的职业机会做好准备。初中和高中学生将接受培训，参加STEM比赛，研究团队将担任科学奥林匹克巡回赛的教练。 该项目的目的是研究软斑片状纳米颗粒（NPs）通过粘蛋白凝胶和溶液进行恒定滑动速度的传输行为。核（金）-（凝胶）壳NP将被使用，其直径为50 nm至150 nm，弹性模量为0.1 kPa至10 kPa，并且表面用胺、羧酸和聚（乙二醇）官能化。纤毛的同步跳动将通过施加生理相关频率为2 Hz至20 Hz的三角形剪切波来模拟。实验将使用涨落相关谱（FCS）测量动态范围内四十年的均方位移随时间的变化。将通过FCS测量的亚微米长度尺度的扩散与通过毛细管渗透实验通过生理相关的较厚粘液层的转运进行比较。将进行相位调制椭圆偏振法、流变学和动态光散射实验以量化颗粒-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粘液的结构，流变学和屏障特性耦合的基本问题。从更广泛的角度来看，所获得的知识将与更好地理解颗粒和大分子在拥挤的生物系统中的运输有关，例如细胞质，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，该奖项反映了NSF的法定使命，并通过使用基金会的智力价值进行评估，被认为值得支持和更广泛的影响审查标准。

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.