The Gardner Laboratory uses a combination experimental and computational approach to dissect molecular mechanisms for how microtubule lengths are regulated inside of cells, and for how force signaling acts to ensure proper chromosome segregation during mitosis. We use biophysical computational modeling to better integrate and understand our experimental observations, make new experimental predictions, and to test whether our proposed cellular mechanisms are physically reasonable. Overall, we are a cellular biophysics laboratory that combines cell biology tools with biophysical methods to shed new light on the regulation of microtubule dynamics, and to dissect forces in mitosis. Achieving the goals described in this application will provide mechanistic insights into how molecular-scale changes in microtubule structure could regulate cellular-scale changes in microtubule-associated protein localization and binding, as well as how changes in chromosome structure and stiffness could affect cellular-level tension signaling during mitosis. In particular, this application will advance our understanding of: 1) how microtubule structure can alter protein binding, and vice versa, 2) how the cell reads out and responds to nuanced tension signaling during mitosis, and 3) how a disease process such as cancer may alter tension signaling during mitosis, and the specific impact of aneuploidy, which is a hallmark of cancer cells, on centromere stiffness and tension signaling during mitosis.