CAREER: Understanding the Structure and Function of the Endothelial Glycocalyx through Single Molecule Visualization

非技术层面血管壁是流动的血液和组织之间的活生生的界面。这种界面含有丰富的聚合物，其特性由人体精心维护和管理，以控制物质从血液流向周围组织的分布。这个项目将应用先进的显微技术来研究材料如何穿过血管壁富含聚合物的界面，并试图建立我们对界面结构及其生物功能的基本理解。这项研究工作与一项教育计划密切相关，该计划旨在为学生开发介于物理科学和生命科学之间的新的实验室体验。该计划的重点是将本科生研究人员纳入概述的研究，开发一门新的实验室课程，以及一系列相关的K-12外联活动。这些努力寻求在生物物理学研究领域、本科生命科学课程和K-12跨课程活动之间建立牢固的联系，以突出材料在生命系统中所起的作用。这个项目将扩大我们对血管壁中富含聚合物界面的基本物理及其在维持血管壁完整性方面的作用的知识。该项目的结果可能导致新的药物输送方法或选择性过滤技术的开发。技术活细胞的机械环境在调节细胞功能和维持组织完整性方面起着至关重要的作用。在维管壁中，一种连接到细胞表面的聚合物刷子，称为糖萼，形成了细胞微环境的关键部分。目前的糖萼模型没有回答关于它们在血管功能中的作用的重要问题。两个特别重要的领域是：(I)当这些刷子暴露在脉动流体流动中时，这些刷子是如何动态构造的，以及(Ii)这如何影响血管系统的关键功能，如从血液到周围组织的物质运输。该项目将使用快速颗粒跟踪和先进的流体流动控制来解决这些问题，以直接可视化纳米颗粒与活细胞的糖基化相互作用的动态。这个项目的主要目标是扩大我们对界面聚合物刷子在维持血管系统的完整性和调节材料从血流到血管壁内皮细胞层的运输方面的作用的理解。这可能导致新的诊断技术来检测血管疾病的早期预警迹象，揭示新的药物输送机制或导致选择性筛选的新方法。这一奖项反映了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。

Non-TechnicalThe blood vessel wall is a living interface between flowing blood and tissue. This interface is rich in polymers, and its properties are meticulously maintained and curated by the body to control the distribution of material from the blood stream into the surrounding tissues. This project will apply advanced microscopy techniques to study how material crosses the polymer rich interface of the blood vessel wall, and seeks to build our basic understanding of structure of the interface and its biological function. The research effort is closely linked to an educational plan that seeks to develop new laboratory experiences for students at the interface between physical and life sciences. This plan is focused on the inclusion of undergraduate researchers in the outlined research, the development of a new laboratory course, and a sequence of related K-12 outreach activities. These endeavors seek to establish strong links between the field of biophysical research, the undergraduate life science curriculum, and K-12 cross-curricular activities to highlight roles played by materials in living systems. This project will expand our knowledge of the basic physics of the polymer rich interface in the blood vessel wall and its role in maintaining the integrity of the blood vessel wall. The results of this project may lead to the development of new drug delivery methods or selective filtering technologies. TechnicalThe mechanical environment of living cells plays an essential role in regulating cell function and maintaining the integrity of tissue. In the vascular wall a polymer brush tethered to the cell surface, known as the glycocalyx, forms a critical part of the cellular microenvironment. Current models of the glycocalyx leave important questions about their role in vascular function unanswered. Two areas of particular importance are: (i) how these brushes are dynamically structured when exposed to pulsatile fluid flow and (ii) how this affects key functions of the vasculature such as material transport from the bloodstream to surrounding tissues. This project will address these questions using fast particle tracking and advanced fluid flow control to directly visualize the dynamics nanoparticles interacting with the glycocalyx of living cells. The primary goal of this project is to expand our understanding of the role of interfacial polymer brushes in maintaining the integrity of the vasculature and regulating material transport from the blood stream to the layer of endothelial cells in the blood vessel wall. This could lead to new diagnostic techniques to detect the early warning signs of vascular disease, reveal new mechanisms for drug delivery or lead to new approaches for selective filtering.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.