Experimental and Computational Models of Bacteria Transport and Adhesion in the Microvasculature

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Bacteria transport in the human circulatory system has important implications in bacteria-mediated cancer therapy and blood-borne bacterial infection. Bacteria in the bloodstream enter into the surrounding tissue through microvasculature or capillary walls. The motion of bacteria in capillaries is influenced by their own self-propulsion, capillary size, the presence of red blood cells in the capillary, and the pressure difference between the capillary and the surrounding tissue. Bacteria also adhere to the capillary wall through various physical and chemical mechanisms. All these factors influence the penetration of bacteria from the bloodstream into the surrounding tissue through the capillary wall. Study of bacteria transport in the human body is very challenging; therefore, this research proposes laboratory experiments and computer modeling of bacteria transport and adhesion in capillaries under physiologically relevant conditions. The methods developed in this research can also be applied to other pathogens such as viruses and fungi, as well as drug delivery agents. The proposed research can significantly impact human health by contributing to the discovery of new drug targets in cancer and infectious diseases in the long term. The proposed research elements will also be integrated into interdisciplinary educational and outreach experiences for K-12, community college, undergraduate, and graduate students to enhance recruitment and retention of the socioeconomically disadvantaged and ethnically underrepresented groups in science, technology, engineering, and mathematics.The goal of this project is to systematically investigate the role of the capillary structure and flow parameters, bacterial motility and adhesive interactions, and transcapillary pressure gradient on the intracapillary transport, margination, and adhesion of bacteria in normal and leaky tumor microvasculature. This goal will be achieved through the following specific aims: (1) Development of physiologically relevant microfluidic and computational models of capillary flow; (2) Investigation of the role of bacteria motility and flagella- and type-1 pili-mediated adhesive interactions with the endothelium in bacteria margination and adhesion to the endothelium; (3) Determination of the role of transcapillary pressure gradient on bacteria transport in normal and leaky tumor microvasculature. The proposed work is transformative as it will create new knowledge about the role of capillary hemodynamics, bacterial motility, and bacteria-host cell interactions in the transport and dissemination of bacteria by establishing a new suite of computational and experimental platforms in Fluid Dynamics.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.