Transport of Virus-like Nanoparticles through Mucus

新冠肺炎是由严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)引起的疾病。这种病毒和许多其他病毒一样，形状几乎是球形的，核心是蛋白质-核酸复合体，周围环绕着蛋白质装饰的脂质双层。病毒降落在呼吸道表面后，需要在密集、粘稠和异质的粘液网络中导航，该粘液网络不断受到纤毛的打击，试图清除被困的病毒。这个实验项目将使用柔软的、片状的纳米颗粒作为病毒粒子，形成凝胶的粘蛋白分子作为粘液屏障，剪切流作为纤毛的搏动。模型系统将捕捉相关的基本物理并产生可重现的结果，这些结果将揭示粒子的软性、粒子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粘液层的传输。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。初中和高中生将接受培训，参加STEM比赛，研究团队将担任科学奥林匹克锦标赛的教练。该项目的目的是研究软片状纳米颗粒(NPs)在恒定滑动速度下通过粘蛋白凝胶和溶液的传输行为。核(金)-(凝胶)壳纳米粒子的直径从50 nm到150 nm，弹性模数从0.1kpa到10kpa，表面使用胺、羧酸和聚乙二醇官能化。通过施加生理相关频率从2赫兹到20赫兹的三角剪切波，将模拟纤毛的同步跳动。实验将利用涨落相关光谱(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渗透实验与生理上相关的较厚粘液层的传输进行比较。将进行位相调制椭偏仪、流变学和动态光散射实验，以量化颗粒与基质的相互作用、网络的粘弹性及其涨落。这项研究将解决纳米尺度的动力学如何与粘液的结构、流变学和阻隔性相结合的基本问题。从更广泛的角度来看，所获得的知识将与更好地了解颗粒和大分子在拥挤的生物系统中的传输相关，如细胞质、微生物生物膜和细胞外基质，以及在各种工程流体中，包括凝胶、乳剂和堵塞的系统。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.