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Elasty movie stabilizer cost5/24/2023 Closely associated with the XO nuclear envelope is a meshwork of primarily B-type lamin filaments ( Lourim and Krohne, 1993), which are conserved in metazoan evolution and essential for mammalian cell viability ( Cohen et al., 2001 Harborth et al., 2001). ![]() Thus the mechanical properties of the XO nuclear envelope are less influenced by chromatin. The Xenopus oocyte (XO) nucleus has a diameter about twenty times larger than typical somatic nuclei, but its chromatin content is similar. Proposed disease mechanisms include defects in tissue-specific gene expression coupled to mechanical weakness of the nuclear envelope ( Morris, 2001 Wilson, 2000 Zastrow et al., 2004). Heterozygous mutations in laminin B receptor (LBR), a membrane protein that binds lamin B, cause the dominant Helger-Puet anomaly of white blood cell nuclear shape homozygous defects in LBR are linked to bone and cartilage disorders and developmental delay ( Hoffmann et al., 2002). These diseases include Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy with conduction system disease ( Burke and Stewart, 2002), and Hutchinson-Gilford progeria syndrome, a devastating `premature aging' syndrome ( De Sandre-Giovannoli et al., 2003 Eriksson et al., 2003). At least eight diseases have been linked to mutations in A-type lamins or lamin-binding proteins of the nuclear inner membrane. Aberrations in nuclear morphology, more than cell morphology, also identify cancerous tissue ( Bissell et al., 1999). Examples include multi-lobed nuclei in neutrophils ( Yabuki et al., 1999) and elongated nuclei in spermatids ( Dadoune, 2003). Although the exact mechanisms governing force transduction are unknown, nuclear envelope stiffness is a hypothesized regulator of the effects of cellular forces on chromatin or gene expression.Īlthough the typical cell nucleus is spheroidal, some differentiated cells undergo dramatic but regulated changes in nuclear morphology. The nuclear envelope also has physical connections to chromatin via lamins, which bind directly to chromatin ( Moir et al., 1995) and to chromatin-binding nuclear membrane proteins ( Burke and Stewart, 2002 Gant and Wilson, 1997). In somatic cells, most nuclear inner membrane proteins are anchored to lamins, which form stable filament networks near the inner nuclear membrane and in the nuclear interior ( Gruenbaum et al., 2003). Models suggest `bridging' interactions by conserved spectrin-repeator Sun-domain-containing proteins situated in both membranes of the nuclear envelope ( Lee et al., 2002 Zhang et al., 2002 Zhen et al., 2002). The nature of this proposed mechanical coupling, particularly across the nuclear envelope, is not yet understood. In endothelial cells, physical force is transmitted via a pathway from integrins to the cytoskeleton to the nuclear envelope and nuclear interior ( Maniotis et al., 1997). Endothelial cells likewise modify gene expression in response to shear stress ( Papadaki and Eskin, 1997). Compression-induced changes in the shapes of chondrocyte nuclei, for example, correlate with changes in cartilage composition and density ( Guilak, 1995). In light of the conservation of B-type lamins in metazoan evolution, the mechanical properties determined in this investigation suggest physical mechanisms by which mutated lamins can either destabilize nuclear architecture or influence nuclear responses to mechanical signals in Emery-Dreifuss muscular dystrophy, cardiomyopathy, progeria syndromes (premature `aging') and other laminopathies.Ĭells respond to mechanical cues from their environment in part through changes in gene expression. ![]() Our results suggest that the nuclear lamina forms a compressed network shell of interconnected rods that is extensible but limited in compressibility from the native state, thus acting as a `molecular shock absorber'. Compared to plasma membranes of cells, the nuclear envelope is much stiffer and more resilient. ![]() Micropipette aspiration of swollen and unswollen nuclear envelopes is also reversible and yields a network elastic modulus, unaffected by nucleoplasm, that averages 25 mN/m. Swelling proves reversible with addition of high molecular mass dextrans. Using isolated Xenopus oocyte nuclei, we have established swelling conditions that separate the intact nuclear envelope (membranes, pore complexes and underlying lamin filament network) from nucleoplasm and the majority of chromatin. Mechanical properties of the nuclear envelope have implications for cell and nuclear architecture as well as gene regulation.
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