In the middle of it all: Mutual mechanical regulation between the nucleus and the cytoskeleton

Dahl, Kris Noel; Booth-Gauthier, Elizabeth A.; Ladoux, Benoît

doi:10.1016/j.jbiomech.2009.09.002

Cited by 55 publications

(54 citation statements)

References 96 publications

(107 reference statements)

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“…Indeed, F-actin is known to be one of the primary determinants of cellular stiffness in most cell types (Pesen and Hoh, 2005;Rotsch and Radmacher, 2000;Wakatsuki et al, 2001), second only to the nuclear lamina (typically ,5-10-fold stiffer than F-actin structures; Caille et al, 2002;Dahl et al, 2010;Dahl et al, 2008). Thus, we postulated that specific subcellular loci for diapedesis would exclude the endothelial nucleus and, in non-nuclear regions, correlate inversely with Factin distribution in endothelial cells.…”

Section: Ilps Might Function In Local Sampling Of Endothelial Stiffnessmentioning

confidence: 83%

Probing the biomechanical contribution of the endothelium to lymphocyte migration: diapedesis by the path of least resistance

Martinelli

Zeiger

Whitfield

et al. 2014

Journal of Cell Science

107

148

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Immune cell trafficking requires the frequent breaching of the endothelial barrier either directly through individual cells ('transcellular' route) or through the inter-endothelial junctions ('paracellular' route). What determines the loci or route of breaching events is an open question with important implications for overall barrier regulation. We hypothesized that basic biomechanical properties of the endothelium might serve as crucial determinants of this process. By altering junctional integrity, cytoskeletal morphology and, consequently, local endothelial cell stiffness of different vascular beds, we could modify the preferred route of diapedesis. In particular, high barrier function was associated with predominantly transcellular migration, whereas negative modulation of junctional integrity resulted in a switch to paracellular diapedesis. Furthermore, we showed that lymphocytes dynamically probe the underlying endothelium by extending invadosome-like protrusions (ILPs) into its surface that deform the nuclear lamina, distort actin filaments and ultimately breach the barrier. Fluorescence imaging and pharmacologic depletion of F-actin demonstrated that lymphocyte barrier breaching efficiency was inversely correlated with local endothelial F-actin density and stiffness. Taken together, these data support the hypothesis that lymphocytes are guided by the mechanical 'path of least resistance' as they transverse the endothelium, a process we term 'tenertaxis'.

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Section: Ilps Might Function In Local Sampling Of Endothelial Stiffnessmentioning

confidence: 83%

Probing the biomechanical contribution of the endothelium to lymphocyte migration: diapedesis by the path of least resistance

Martinelli

Zeiger

Whitfield

et al. 2014

Journal of Cell Science

107

148

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“…If oscillatory accelerations and resultant motions can modulate mechanotransduction, cellular ultrastructural elements will be an important determinant for the transfer of prescribed motion, since transduction of mechanical signals in cells is mainly dependent on the cytoskeletal network (Ingber, 1997(Ingber, , 2003bDahl et al, 2010). Consistent with the idea that cytoskeletal elements are strong determinants of mechanotransductive pathways, chemical blocking of actin polymerization inhibits the response of bone cells to mechanical stimulation (Rosenberg, 2003).…”

Section: Introductionmentioning

confidence: 92%

Bone marrow stem cells adapt to low-magnitude vibrations by altering theircytoskeleton during quiescence and osteogenesis

Demiray¹,

Özçivici

2015

Turk J Biol

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Application of mechanical vibrations is anabolic to bone tissue, not only by guiding mature bone cells to increased formation, but also by increasing the osteogenic commitment of progenitor cells. However, the sensitivity and adaptive response of bone marrow stem cells to this loading regimen has not yet been identified. In this study, we subjected mouse bone marrow stem cell line D1-ORL-UVA to daily mechanical vibrations (0.15 g, 90 Hz, 15 min/day) for 7 days, both during quiescence and osteogenic commitment, to identify corresponding ultrastructural adaptations on cellular and molecular levels. During quiescence, mechanical vibrations significantly increased total actin content and actin fiber thickness, as measured by phalloidin staining and fluorescent microscopy. Cellular height also increased, as measured by atomic force microscopy, along with the expression of focal adhesion kinase (PTK2) mRNA levels. During osteogenesis, mechanical vibrations increased the total actin content, actin fiber thickness, and cytoplasmic membrane roughness, with significant increase in Runx2 mRNA levels. These results show that bone marrow stem cells demonstrate similar cytoskeletal adaptations to low-magnitude high-frequency mechanical loads both during quiescence and osteogenesis, potentially becoming more sensitive to additional loads by increased structural stiffness.

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“…That these groups are most perturbed is perhaps unsurprising: the nucleus is known to be an important mechanical component of the cell, with the lamins interfacing with other structural components through the LINC (linker of nucleoskeleton and cytoskeleton) complex. 48 It has been reported that lamin-A,C level can influence actin-bundling proteins such as T-plastin. 29 Many cytoskeletal proteins are regulated by the SRF pathway, 49 which itself is influenced by actin, known to interact directly with lamin-A,C 50 and other nuclear proteins such as emerin.…”

Section: Proteome Profiling Following Lamin Kd In A549 and Mscsmentioning

confidence: 99%

Label-free mass spectrometry exploits dozens of detected peptides to quantify lamins in wildtype and knockdown cells

Swift

Harada

Buxboim

et al. 2013

Nucleus

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L abel-free quantitation and characterization of proteins by mass spectrometry (ms) is now feasible, especially for moderately expressed structural proteins such as lamins that typically yield dozens of tryptic peptides from tissue cells. using standard cell culture samples, we describe general algorithms for quantitative analysis of peptides identified in liquid chromatography tandem mass spectrometry (Lc-ms/ms). the algorithms were foundational to the discovery that the absolute stoichiometry of a-type to b-type lamins scales with tissue stiffness (swift et al., Science 2013). isoform dominance helps make sense of why mutations and changes with age of mechanosensitive lamin-a,c only affect "stiff" tissues such as heart, muscle, bone, or even fat, but not brain. a peak ratio fingerprinting (prf) algorithm is elaborated here through its application to lamin-a,c knockdown. after demonstrating the large dynamic range of prf using calibrated mixtures of human and mouse lysates, we validate measurements of partial knockdown with standard cell biology analyses using quantitative immunofluorescence and immunoblotting. optimal sets of ms-detected peptides as determined by prf demonstrate that the strongest peptide signals are not necessarily the most reliable for quantitation. after lamin-a,c knockdown, prf computes an invariant set of "housekeeping" proteins as part of a broader proteomic analysis that also shows the proteome of mesenchymal stem cells (mscs) is more broadly perturbed than that of a human epithelial cancer line (a549s), with particular variation in nuclear and cytoskeletal proteins. these methods offer exciting prospects for basic and clinical studies of lamin-a,c as well as other ms-detectable proteins.

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In the middle of it all: Mutual mechanical regulation between the nucleus and the cytoskeleton

Cited by 55 publications

References 96 publications

Probing the biomechanical contribution of the endothelium to lymphocyte migration: diapedesis by the path of least resistance

Probing the biomechanical contribution of the endothelium to lymphocyte migration: diapedesis by the path of least resistance

Bone marrow stem cells adapt to low-magnitude vibrations by altering theircytoskeleton during quiescence and osteogenesis

Label-free mass spectrometry exploits dozens of detected peptides to quantify lamins in wildtype and knockdown cells

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