scholarly journals Nuclear lamin isoforms differentially contribute to LINC complex-dependent nucleocytoskeletal coupling and whole cell mechanics

2021 ◽  
Author(s):  
Amir Vahabikashi ◽  
Suganya Sivagurunathan ◽  
Fiona Ann Sadsad Nicdao ◽  
Yu Long Han ◽  
Chan Young Park ◽  
...  

The ability of a cell to regulate its mechanical properties is central to its function. Emerging evidence suggests that interactions between the cell nucleus and cytoskeleton influence cell mechanics through poorly understood mechanisms. Here we show that A- and B-type nuclear lamin isoforms distinctively modulate both nuclear and cellular volume and selectively stabilize the linker of nucleoskeleton and cytoskeleton (LINC) complexes that couple the nucleus to cytoskeletal actin and vimentin. We reveal, further, that loss of each of the four-known lamin isoforms in the mouse embryonic fibroblasts differentially affects cortical and cytoplasmic stiffness as well as cellular contractility, and then propose a LINC complex mediated model that explains these impaired mechanical phenotypes. Finally, we demonstrate that loss of each lamin isoform softens the nucleus in a manner that correlates with loss of heterochromatin. Together, these findings uncover distinctive roles for each lamin isoform in maintaining cellular and nuclear mechanics.

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e84062 ◽  
Author(s):  
Yu-Cheng Tu ◽  
Duen-Yi Huang ◽  
Shine-Gwo Shiah ◽  
Jang-Shiun Wang ◽  
Wan-Wan Lin

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1534
Author(s):  
Krystyna Żyżyńska-Galeńska ◽  
Jolanta Karasiewicz ◽  
Agnieszka Bernat

We would like to address the issues raised by Pierre Savatier in “Introduction of Mouse Embryonic Fibroblasts into Early Embryos Causes Reprogramming and (Con)Fusion” [...]


2008 ◽  
Vol 134 (4) ◽  
pp. A-86
Author(s):  
Engda G. Hagos ◽  
Amr Ghaleb ◽  
W Brian Dalton ◽  
Jonathan P. Katz ◽  
Klaus H. Kaestner ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 851
Author(s):  
Veronika Pfannenstill ◽  
Aurélien Barbotin ◽  
Huw Colin-York ◽  
Marco Fritzsche

Mechanobiology seeks to understand how cells integrate their biomechanics into their function and behavior. Unravelling the mechanisms underlying these mechanobiological processes is particularly important for immune cells in the context of the dynamic and complex tissue microenvironment. However, it remains largely unknown how cellular mechanical force generation and mechanical properties are regulated and integrated by immune cells, primarily due to a profound lack of technologies with sufficient sensitivity to quantify immune cell mechanics. In this review, we discuss the biological significance of mechanics for immune cells across length and time scales, and highlight several experimental methodologies for quantifying the mechanics of immune cells. Finally, we discuss the importance of quantifying the appropriate mechanical readout to accelerate insights into the mechanobiology of the immune response.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christian Aermes ◽  
Alexander Hayn ◽  
Tony Fischer ◽  
Claudia Tanja Mierke

AbstractThe knowledge of cell mechanics is required to understand cellular processes and functions, such as the movement of cells, and the development of tissue engineering in cancer therapy. Cell mechanical properties depend on a variety of factors, such as cellular environments, and may also rely on external factors, such as the ambient temperature. The impact of temperature on cell mechanics is not clearly understood. To explore the effect of temperature on cell mechanics, we employed magnetic tweezers to apply a force of 1 nN to 4.5 µm superparamagnetic beads. The beads were coated with fibronectin and coupled to human epithelial breast cancer cells, in particular MCF-7 and MDA-MB-231 cells. Cells were measured in a temperature range between 25 and 45 °C. The creep response of both cell types followed a weak power law. At all temperatures, the MDA-MB-231 cells were pronouncedly softer compared to the MCF-7 cells, whereas their fluidity was increased. However, with increasing temperature, the cells became significantly softer and more fluid. Since mechanical properties are manifested in the cell’s cytoskeletal structure and the paramagnetic beads are coupled through cell surface receptors linked to cytoskeletal structures, such as actin and myosin filaments as well as microtubules, the cells were probed with pharmacological drugs impacting the actin filament polymerization, such as Latrunculin A, the myosin filaments, such as Blebbistatin, and the microtubules, such as Demecolcine, during the magnetic tweezer measurements in the specific temperature range. Irrespective of pharmacological interventions, the creep response of cells followed a weak power law at all temperatures. Inhibition of the actin polymerization resulted in increased softness in both cell types and decreased fluidity exclusively in MDA-MB-231 cells. Blebbistatin had an effect on the compliance of MDA-MB-231 cells at lower temperatures, which was minor on the compliance MCF-7 cells. Microtubule inhibition affected the fluidity of MCF-7 cells but did not have a significant effect on the compliance of MCF-7 and MDA-MB-231 cells. In summary, with increasing temperature, the cells became significant softer with specific differences between the investigated drugs and cell lines.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 772
Author(s):  
Pierre Savatier

The reprogramming of somatic cell nuclei to achieve pluripotency is one of the most important biological discoveries of the last few decades [...]


2006 ◽  
Vol 84 (3-4) ◽  
pp. 287-297 ◽  
Author(s):  
Fernand Gobeil ◽  
Audrey Fortier ◽  
Tang Zhu ◽  
Michela Bossolasco ◽  
Martin Leduc ◽  
...  

G-protein-coupled receptors (GPCRs) comprise a wide family of monomeric heptahelical glycoproteins that recognize a broad array of extracellular mediators including cationic amines, lipids, peptides, proteins, and sensory agents. Thus far, much attention has been given towards the comprehension of intracellular signaling mechanisms activated by cell membrane GPCRs, which convert extracellular hormonal stimuli into acute, non-genomic (e.g., hormone secretion, muscle contraction, and cell metabolism) and delayed, genomic biological responses (e.g., cell division, proliferation, and apoptosis). However, with respect to the latter response, there is compelling evidence for a novel intracrine mode of genomic regulation by GPCRs that implies either the endocytosis and nuclear translocation of peripheral-liganded GPCR and (or) the activation of nuclearly located GPCR by endogenously produced, nonsecreted ligands. A noteworthy example of the last scenario is given by heptahelical receptors that are activated by bioactive lipoids (e.g., PGE2 and PAF), many of which may be formed from bilayer membranes including those of the nucleus. The experimental evidence for the nuclear localization and signalling of GPCRs will be reviewed. We will also discuss possible molecular mechanisms responsible for the atypical compartmentalization of GPCRs at the cell nucleus, along with their role in gene expression.


Sign in / Sign up

Export Citation Format

Share Document