This work integrates an immuno-engineering research program exploring immune cell modulation by mechanical forces with an educational program that targets under-served high school students and teachers. The research objective of this proposal is to investigate the functional modulation of a key immune cell, the dendritic cell (DC), in response to cyclic mechanical strain in combination with adhesion to adhesive proteins commonly used in tissue-engineered constructs. We will elucidate key signal transduction elements in DC responses to mechanical forces. The central hypothesis is that DCs incorporate mechanical strain as an integral signal contributing to both physiological (homeostasis/tolerance) and pathological (adaptive response to self-antigen) immune processes of the vascular wall. Dysregulation of this biomechanical input can thereby disrupt immune homeostasis, breaking peripheral tolerance through the DC-directed activation of T cells and initiating adaptive immune responses to self-antigens or to biological components of tissue-engineered constructs. While it is established that other vascular wall cell-types respond to mechanical strain, investigation of the mechanical strain-modulation of DCs is novel.
A fundamental understanding of how immune cell responses are modulated by biomechanical forces such as those seen in the vascular wall is critical to the advancement of vascular wall biology and vascular tissue engineering, substantiating the broad impact of this work. The educational objective is to motivate and stimulate students and teachers of under-served high schools toward more efficient learning by a combination of hands-on application of biomedical engineering concepts in the laboratory and internet-based tutorials.
