Regulation of Myometrial Smooth Muscle Contractility by Mechanical Stretch and Mechanoinflammation

Many cells in the body, including muscle cells and immune cells, react to stretch. The myometrium is the smooth muscle layer of the uterus, the organ that supports the development of a fetus during a pregnancy. The goal of this research is to determine the impact of varying amounts of stretch on the contraction of muscle cells isolated from the human uterus, including identifying the parts of cells that respond to stretch and the influence of nearby immune cells. Project outcomes intend to include a deeper understanding of the impact of stretch on uterine contractions and the discovery of new pathways that could be modified in patients to help treat pregnancy-related complications. This project will also support the training of graduate and undergraduate students and on-site field trips to the lab for local high school students. This project looks to determine how mechanical stretch directly impacts the contractility of human smooth muscle cells isolated from the myometrium, the muscular layer of the uterus. The research team will engineer human myometrial smooth muscle cells into aligned microtissues, stretch them to various extents, and quantify changes to their physiology and transcriptome to identify potential mechanisms of mechanosensing. Further, the research project will test if mechanical stretch induces myometrial smooth muscle cells and/or macrophages to secrete pro-inflammatory factors that activate contractile responses. The research team will engineer a device to co-culture stretched and un-stretched cells and use it to evaluate the impact of crosstalk between (un)stretched macrophages and myometrial smooth muscle cells. Together, the project seeks to advance fundamental knowledge of how both stretch and inflammation regulate myometrial contractility that may inform new therapeutic approaches. The PI will also train graduate students who will enter the biomedical workforce and expose local high school students to the discipline of biomedical engineering. 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.