This award supports research that studies how tissues modify their structure over time and how these changes are influenced by mechanical loading. The research focuses on the aortic valve leaflet, a vital part of the heart that opens and closes to control blood flow. The cells in the leaflet are constantly remodeling: building, breaking down, and rearranging the supportive material around them—based on various stimuli, including mechanical loading. However, these structural changes also affect the mechanical loading on the leaflet, creating a feedback loop that is not yet fully understood. In calcific valve disease, this process leads to the thickening and hardening of the leaflet, preventing it from opening properly. This increases the workload on the heart, ultimately leading to heart failure. To investigate this feedback loop, this project will: 1) Develop a new method to measure how the material properties of the leaflet vary across its surface and over time and 2) Use advanced imaging techniques to study the leaflet's structure at different scales, particularly around small calcium deposits (microcalcifications) that stiffen the valve and reduce its function. The developed technology and research findings will also enable future studies aimed at slowing, stopping, or even reversing the formation and growth of microcalcifications. This work will help to elucidate the role of mechanics during aortic valve leaflet remodeling. Remodeling is a continuous process: as cells