ORCID Profile
0000-0002-5275-8038
Current Organisation
National Institutes of Health
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Publisher: Cold Spring Harbor Laboratory
Date: 19-01-2020
DOI: 10.1101/2020.01.18.911529
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.
Publisher: Elsevier BV
Date: 02-2020
Publisher: Cold Spring Harbor Laboratory
Date: 02-09-2020
DOI: 10.1101/2020.09.02.276071
Abstract: Speech perception requires the binding of spatiotemporally disjoint auditory–visual cues. The corresponding brain network-level information can be characterized by two complementary mechanisms, functional segregation which refers to the localization of processing, and integration which pertains to cooperation among relevant functional modules. Here, we demonstrate using fMRI recordings that subjective perceptual experience of multisensory speech stimuli, real and illusory, are represented in differential states of segregation–integration balance. We controlled the inter-subject variability of illusory/cross-modal perception parametrically, by introducing temporal lags in the incongruent auditory–visual articulations of speech sounds using the McGurk paradigm. The functional segregation–integration balance was captured using two alternative computational approaches. First, the module responsible for cross-modal binding of sesnory signals defined as the perceptual binding network (PBN) was identified using standardized parametric statistical approaches and their temporal correlations with all other brain areas were computed. With increasing illusory perception, the majority of the nodes of PBN showed decreased cooperation with the rest of the brain, reflecting high local segregation but reduced global integration. Second, using graph theoretic measures, the altered patterns of local segregation–global integration were cross-validated.
Publisher: Public Library of Science (PLoS)
Date: 09-10-2020
Publisher: Elsevier BV
Date: 02-2019
Publisher: The Company of Biologists
Date: 12-2021
DOI: 10.1242/JCS.258581
Abstract: The mechanisms by which the mechanoresponsive actin crosslinking protein α-actinin-4 (ACTN4) regulates cell motility and invasiveness remain incompletely understood. Here, we show that, in addition to regulating protrusion dynamics and focal adhesion formation, ACTN4 transcriptionally regulates expression of non-muscle myosin IIB (NMM IIB heavy chain encoded by MYH10), which is essential for mediating nuclear translocation during 3D invasion. We further show that an indirect association between ACTN4 and NMM IIA (heavy chain encoded by MYH9) mediated by a functional F-actin cytoskeleton is essential for retention of NMM IIA at the cell periphery and modulation of focal adhesion dynamics. A protrusion-dependent model of confined migration recapitulating experimental observations predicts a dependence of protrusion forces on the degree of confinement and on the ratio of nucleus to matrix stiffness. Together, our results suggest that ACTN4 is a master regulator of cancer invasion that regulates invasiveness by controlling NMM IIB expression and NMM IIA localization. This article has an associated First Person interview with the first author of the paper.
Publisher: Springer Science and Business Media LLC
Date: 09-08-2016
DOI: 10.1038/SREP31280
Abstract: Multisensory processing involves participation of in idual sensory streams, e.g., vision, audition to facilitate perception of environmental stimuli. An experimental realization of the underlying complexity is captured by the “McGurk-effect”- incongruent auditory and visual vocalization stimuli eliciting perception of illusory speech sounds. Further studies have established that time-delay between onset of auditory and visual signals (AV lag) and perturbations in the unisensory streams are key variables that modulate perception. However, as of now only few quantitative theoretical frameworks have been proposed to understand the interplay among these psychophysical variables or the neural systems level interactions that govern perceptual variability. Here, we propose a dynamic systems model consisting of the basic ingredients of any multisensory processing, two unisensory and one multisensory sub-system (nodes) as reported by several researchers. The nodes are connected such that biophysically inspired coupling parameters and time delays become key parameters of this network. We observed that zero AV lag results in maximum synchronization of constituent nodes and the degree of synchronization decreases when we have non-zero lags. The attractor states of this network can thus be interpreted as the facilitator for stabilizing specific perceptual experience. Thereby, the dynamic model presents a quantitative framework for understanding multisensory information processing.
Publisher: Frontiers Media SA
Date: 13-10-2016
Publisher: ASME International
Date: 22-02-2021
DOI: 10.1115/1.4049906
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.
Publisher: Springer Science and Business Media LLC
Date: 11-02-2022
Location: India
No related grants have been discovered for Abhishek Mukherjee.