Abstract: Large nuclear deformations during migration through confined spaces have been associated with nuclear membrane rupture and DNA damage. However, the stresses associated with nuclear damage remain unclear. Here, using a quasi-static plane strain finite element model, we map evolution of nuclear shape and stresses during confined migration of a cell through a deformable matrix. Plastic deformation of the nucleus observed for a cell with stiff nucleus transiting through a stiffer matrix lowered nuclear stresses, but also led to kinking of the nuclear membrane. In line with model predictions, transwell migration experiments with fibrosarcoma cells showed that while nuclear softening increased invasiveness, nuclear stiffening led to plastic deformation and higher levels of DNA damage. In addition to highlighting the advantage of nuclear softening during confined migration, our results suggest that plastic deformations of the nucleus during transit through stiff tissues may lead to bending-induced nuclear membrane disruption and subsequent DNA damage.

Abstract: A physician palpates a tissue to detect an embedded tumor nodule by sensing an increase in local tissue stiffness and nodule size. The Hertz contact model however, is unable to predict the material or physical properties of a tumor nodule embedded in a healthy tissue of finite thickness. In this study, utilizing a hyperelastic material model, we propose a general methodology to analyze the extent to which the stiffness, size and depth of a nodule embedded in a tissue affect its detectability. Using dimensional analysis, we generate simple power-law relations to predict physical and material properties of tumor nodules embedded in healthy tissue during indentation. Our results indicate that indenter radius and indentation depth are critical parameters in nodule detection and a thin indenter and large indentation depth increase detection sensitivity of an embedded tumor nodule. Our results also show that anisotropic material properties of either a tissue or an embedded nodule render the embedded tumor nodule undetectable using indentation. We define palpation sensitivity maps that can be used to predict material and physical properties of tumor nodules in healthy tissues. The analysis and results presented in this study might increase accuracy and precision in instrumented probe-based laparoscopic or robotic surgeries.

Abstract: In daily lives, speech perception requires binding of spatiotemporally disjoint auditory and visual cues. On the other hand, functional segregation and integration are the two complementary mechanisms that capture brain information processing. Here, we demonstrate using fMRI recordings that subjective perceptual experience of multisensory speech stimuli is dependent on a homeostatic balance of segregation and integration mechanisms. Previous reports conceptualized posterior superior temporal sulcus as the key brain region for binding signals from multiple sensory streams. However, we report an enhancement of segregated information processing in distributed brain regions, defined as the perceptual binding network. The seed-based whole brain functional connectivity of each node in this network was anti-correlated with higher propensity for illusory perception. Interestingly, the perceptual binding network was anti-correlated with other intrinsic brain networks, such as dorsal attention and default mode networks during cross-modal perception. The pattern disappeared for people who rarely reported the illusory perception, further strengthening the hypothesis of homeostatic balance. The cognitive theories of Bayesian causal inference and predictive coding hypothesis could explain the balance of segregative and integrative mechanisms during cross-modal perception.