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

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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.