Deformation of the nucleus by TGFβ1 via the remodeling of nuclear envelope and histone isoforms

The cause of nuclear shape abnormalities which are often seen in pre-neoplastic and malignant tissues is not clear. In this study we report that deformation of the nucleus can be induced by TGFβ1 stimulation in several cell lines including Huh7. In our results, the upregulated histone H3.3 expression downstream of SMAD signaling contributed to TGFβ1-induced nuclear deformation, a process of which requires incorporation of the nuclear envelope (NE) proteins lamin B1 and SUN1. During this process, the NE constitutively ruptured and reformed. Contrast to lamin B1 which was relatively stationary around the nucleus, the upregulated lamin A was highly mobile, clustering at the nuclear periphery and reintegrating into the nucleoplasm. The chromatin regions that lost NE coverage formed a supra-nucleosomal structure characterized by elevated histone H3K27me3 and histone H1, the formation of which depended on the presence of lamin A. These results provide evidence that shape of the nucleus can be modulated through TGFβ1-induced compositional changes in the chromatin and nuclear lamina.

Mechanics-driven nuclear localization of YAP can be reversed by N-cadherin ligation in mesenchymal stem cells

Mesenchymal stem cells adopt differentiation pathways based upon cumulative effects of mechanosensing. A cell’s mechanical microenvironment changes substantially over the course of development, beginning from the early stages in which cells are typically surrounded by other cells and continuing through later stages in which cells are typically surrounded by extracellular matrix. How cells erase the memory of some of these mechanical microenvironments while locking in memory of others is unknown. Here, we develop a material and culture system for modifying and measuring the degree to which cells retain cumulative effects of mechanosensing. Using this system, we discover that effects of the RGD adhesive motif of fibronectin (representative of extracellular matrix), known to impart what is often termed “mechanical memory” in mesenchymal stem cells via nuclear YAP localization, are erased by the HAVDI adhesive motif of the N-cadherin (representative of cell-cell contacts). These effects can be explained by a motor clutch model that relates cellular traction force, nuclear deformation, and resulting nuclear YAP re-localization. Results demonstrate that controlled storage and removal of proteins associated with mechanical memory in mesenchymal stem cells is possible through defined and programmable material systems.

Deformation of the Nucleus by TGFβ1 Via the Remodeling of Nuclear Envelope and Histone Isoforms

The cause of nuclear shape abnormalities which are often seen in pre-neoplastic and malignant tissues is not clear. In this study we report that deformation of the nucleus can be induced by TGFb1 stimulation in several cell lines including Huh7. In our results, the upregulated histone H3.3 expression downstream of SMAD signaling contributed to TGFb1-induced nuclear deformation, a process of which requires incorporation of the nuclear envelope (NE) proteins lamin B1 and SUN1. During this process, the NE constitutively ruptured and reformed with no observable indications of DNA damage response. Contrast to lamin B1 which was relatively stationary around the nucleus, the upregulated lamin A was highly mobile, shuttling between the nucleus and cytoplasm, and clustering at the nuclear periphery. The chromatin regions that lost NE coverage formed a supra-nucleosomal structure characterized by elevated histone H3K27me3 and histone H1, the formation of which depended on the presence of lamin A. These results provide evidence that shape of the nucleus can be modulated through TGFb1-induced compositional changes in the chromatin and nuclear lamina.

Impact of Nuclear Deformation on Neutron Dripline Prediction: A Study of Mg Isotopes

We have employed the relativistic Hartree-Bogoliubov (RHB) model with density-dependent meson-exchange interaction and separable pairing to investigate neutron dripline mechanisms for heavy Mg isotopes. In the present study, 40Mg is predicted to be dripline nuclei. The calculations are carried out by taking axial deformation into account. An investigation of shape transition is also done for even-even 32-42Mg isotopes. Our prediction for neutron dripline for 40Mg is consistent with some recent studies.

Effects of Exogenous Regulation of Ethylene and Abscisic Acid on Grain-Filling and Endosperm PCD of Wheat Under Drought Stress After Anthesis

Although studies have shown that grain-filling and programmed cell death of wheat endosperm are affected by drought stress, which is closely related to ethylene and abscisic acid.The mechanism of ethylene and abscisic acid regulate grain-filling and endosperm PCD under drought stress is remains unclear. In this study, we regulated the production of ethylene and abscisic acid in wheat grains under drought stress at filling stage by chemicals. The results showed that spraying ethylene synthesis inhibitor enhanced endosperm cell viability, delayed nuclear deformation, and decreased ACC content. Compared with the CK, the CN significantly decreased the DNA hydrolase activity and significantly increased the DNA content. In addition, the CN treatment reduced the expression of four genes related to ethylene receptors (ers1, ers2 etr1, etr2) and increase the expression of dad1. Under CN treatment, the process of endosperm PCD was delayed, the duration of high grouting rate was prolonged, and the grain weight was increased, in contrast, the opposite result was obtained after spraying abscisic acid synthesis inhibitor. The production of abscisic acid and ethylene in grains determines the fate of endosperm cells. A new model of artificial regulation of abscisic acid and ethylene, delaying endosperm PCD process and increasing grain weight under post-anthesis drought was proposed.

Perspective: The Mechanobiology of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the second most deadly primary cancer in the world and is thus a major global health challenge. HCC primarily develops in patients with an underlying chronic liver disease, the vast majority with advanced cirrhosis, characterized by increased matrix deposition and liver stiffness. Liver stiffness is highly associated with cancer development and poor patient outcome and is measured clinically to assess cancer risk; cirrhotic livers greatly exceed the threshold stiffness shown to alter hepatocyte cell behavior and to increase the malignancy of cancer cells. Recent studies have shown that cirrhotic liver cells have highly irregular nuclear morphologies and that nuclear deformation mediates mechanosensitive signaling. Separate research has shown that nuclear deformation can increase genetic instability and the accumulation of DNA damage in migrating cancer cells. We hypothesize that the mechanical changes associated with chronic liver disease are drivers of oncogenesis, activating mechanosensitive signaling pathways, increasing rates of DNA damage, and ultimately inducing malignant transformation.