In recent years, scientists have identified special regions of tissues -- known as niches -- within the human body that help sustain and rejuvenate it. These tissue regions contain specialized units called stem cells that provide new life and support to tissues as we grow and age. The stem cells reside locally within the tissues. The tissue acts like a parent to a child - it provides a nurturing environment to live. When the time is right, the environment signals the stem cells to move out and support the surrounding community. However, with disease or with aging, stem cells do not have the same survival or supportive response. It is not known how changes that occur in the stem cells' environment influences their response. In the brain, stem cells reside in a complex environment, directly interacting with other cells, blood vessels, and the surrounding matrix, each of which provides its own influence over the stem cells. The goal of this research is to understand how specific changes in the matrix environment alter the neural stem cell response. The results will be used to better inform how changes in the brain that occur with disease or aging can influence the neural stem cells. This would then allow for better design therapies to sustain stem cell support of the brain. Through both hands-on involvement and the analysis of images, engineering students, high school students, and middle school students will become more engaged in integrating the topics of mechanics, materials, and biomedicine through computer analysis and statistics involved with imaging. Student involvement in research is key to this engagement, and the PI will continue to have students of all ages supporting the research goals of the project.
The overall goal of this research is to investigate the role of mechanotransduction in maintenance and neurogenesis of neural stem cells in order to identify the critical components involved with physiological changes to the neural stem cell niche. It is hypothesized that stem cell maintenance and differentiation are instructed through mechanotransduction by the matrix and cells. This hypothesis will be addressed through two aims. First, by determining how engaging integrin receptors and mechanotransduction signaling pathway alter neural stem cell maintenance and neurogenesis. Second, by determining how cadherin mechanotransduction alters the maintenance and neurogenesis of neural stem cells. These aims will involve the use of microgel-based scaffolds that allow the decoupling of scaffold elasticity from peptide concentration, isolating changes in the mechanical environment from the biochemical environment. Activation of integrins and cadherins will be characterized through various molecules that relate to the mechanocoupling between a cell and its environment or act as mechanical transducers.
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.