Intracellular transport involves movement of molecules and organelles through the subcellular environment and is critical for proper cell function. It can be driven by molecular motors or by cytoskeletal fluctuations and flow of the cytoplasm. Transport plays an integral role in many cellular functions, including migration and division, which are intimately linked to the metastatic spread of cancer. Transport of intracellular components requires interaction with the cytoskeleton in the bulk cytoplasm as well as the cell cortex. Cells also respond to their surrounding physical environment by changing shape and reorganizing their internal structures via passive and active processes. Thus, the interplay between the cell cortex and the bulk cytoskeleton is a key factor in understanding intracellular transport. However, the cytoskeleton-cortex interaction and its role in cell mechanics is not well understood.To this end, we propose a project to characterize the mechanics of the cytoskeleton-cortex interaction in biomimetic and living systems. We focus on three main questions: (1) What is the purely physical change in the actin cytoskeleton in response geometric confinement? (2) What is the role of active processes in structural reorganization? (3) How does the active reorganization of a living cell contribute to intracellular transport? The structural reorganization of the actin cytoskeleton will be measured via confocal imaging and subcellular transport or flow will be quantified by single particle tracking of tracers/organelles. The mechanics of the bulk cytoskeleton and actin cortex will be measured using active microrheology and fluctuation spectroscopy, respectively. This study will uncover how the cytoskeleton-cortex interaction dictates cell mechanics and its contribution to intracellular transport. Our results will lead to a better understanding of how mechanics affects cell motility and division, and has potential to lead to new clinical treatments for cancer