I will describe two experiments that rely on novel live-cell image analysis methodologies. The first examines the role of chromatin-nuclear envelope attachments in determining mechanical properties of the nucleus. In higher eukaryotes, the nuclear lamina is thought to be the nucleus’ primary mechanical defense. However, the lamina is integrated within a network of lipids, proteins, and chromatin; the interdependence of this network poses a challenge to defining the individual mechanical contributions of these components. By employing a system lacking lamins, namely fission yeast, we isolate the role of chromatin in nuclear mechanics.  Specifically, a new image analysis method permits us to observe that untethering chromatin from the inner nuclear membrane results in highly deformable nuclei in vivo, particularly in response to cytoskeletal forces. Using optical tweezers, we find correspondingly that isolated nuclei lacking inner nuclear membrane tethers are also less stiff than wild type nuclei. The second project involves some elegant new statistical tools for analyzing the diffusion of thousands of individual molecules inside living cells, and new ways of conceptualizing these data, with the eventual goal of being able to characterize processes and biochemistry, occurring inside living cells.