Mechanical signaling is critical to the coordinated development and evolution of cells. A failure to respond appropriately to mechanical stress can have dire consequences from cellular apoptosis to malignant features such as cancer. At each stage of the cellular architecture, from the cell membrane to the nuclear core, an interconnected network of physical structures are present that could, in principle, allow mechanical signals to regulate gene expression without a biochemical intermediary. Moreover, we have a limited understanding of how internal forces applied to the DNA, resulting from cellular activity and repeated interaction with the chromosome, affect genetic function. There is, therefore, a need to incorporate DNA mechanics into our understanding of genetic regulation, yet efforts to uncover such biomechanical effects are still in their infancy. I will discuss a series of experiments that could help elucidate the importance of a variety of mechanical effects upon genetic expression within living cells. Furthermore, I will address the need to combine plasmonics with traditional optical trapping techniques to allow single-molecule techniques to probe in vivo cellular processes. Josh Milstein is a post-doc at the University of Michigan. He obtained his Ph.D. degree in Physics from the University of Colorado, Boulder in 2004.