Fluid (blood) and solid (blood vessel wall) forces are both part of the natural mechanical environment of blood vessels and determine blood vessel function. Changes in the properties of blood vessels -- often due to age or disease - can influence the activity of the cells that line the blood vessels (endothelial cells), which can subsequently respond and further affect the properties of the vessel. This Faculty Early Career Development Program (CAREER) research project will test a two-tier hypothesis to further understand this interaction. First, it is hypothesized that the fluid and solid forces work together to regulate behavior of the endothelial cells that line the blood vessel wall. These cells detect these forces, and, in response, guide blood vessel function to maintain health. Second, it is hypothesized that the biological response to force by the endothelial cells (a process called mechanobiology) occurs via the glycocalyx, which is a sugar layer that is anchored to and coats endothelial cells. This CAREER research project will address a critical gap in knowledge about how these vascular lining cells respond to their mechanical environment, a knowledge gap which has limited the success of vascular disease prevention and treatment. New knowledge will make it possible to engineer innovative approaches to control endothelial cell mechanobiology and transform how we repair or regenerate endothelial cell function in blood vessels. STEM (science, technology, engineering, and math) education and outreach activities will be integrated with the research in a manner that will positively impact both mechanobiology research and the STEM workforce. General and underrepresented minority populations of K -12, undergraduate, masters, and doctoral students will be engaged and trained through experiential learning activities -- ranging from hands on challenges for K-3 students to science fair projects to dissertations -- which will be catalyzed by the CAREER research project. The principal investigator will serve as an underrepresented minority coach, and opportunities will also be provided for older students to mentor younger students. This goal of the educational portion of this project is to, in the near future, expand STEM education at all levels and, in the long-term future, expand the diversity of the STEM workforce to enhance innovation.
The overall research goal of this project is to define the endothelial cell and glycocalyx mechanisms of blood vessel regulation through mechanobiology. Three objectives have been established. First, to characterize the architecture of the glycocalyx over a range of combined fluid-solid mechanical stimuli. Second, to link the mechanically-controlled architecture of the glycocalyx to the activation of both protagonist and antagonist molecular mechanisms that drive the response of endothelial cells. And finally, to clarify the extent to which cooperative mechanical, glycocalyx, and molecular stimuli evoke a response within the endothelial cells that impacts blood vessel function. The overall educational objective of this CAREER proposal is to coach and champion culturally diverse students to broaden the future workforce, leverage new perspectives, and enhance endothelial cell mechanobiology research innovation. This will be approached by building an inclusive STEM community that includes research experiences, mentoring, and financial support for graduate, undergraduate, and high school students -- with special emphasis on students from underrepresented groups -- who then reach back to K-8 students to excite them about STEM.
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.
