scholarly journals Mechanical counterbalance of kinesin and dynein motors in microtubular network regulates cell mechanics, 3D architecture, and mechanosensing

2021 ◽  
Author(s):  
Alexander S Zhovmer ◽  
Alexis Manning ◽  
Chynna Smith ◽  
James B Hayes ◽  
Dylan Tyler Burnette ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Mechanics ◽  
Contact Guidance ◽  
Cell Cortex ◽  
Cell Microenvironment ◽  
Septin 9 ◽  
Motor Activities ◽  
3D Architecture ◽  
Microtubular Network ◽  
3D Networks

Microtubules (MTs) and MT motor proteins form active 3D networks made of unstretchable cables with rod-like bending mechanics that provide cells with a dynamically changing structural scaffold. In this study, we report an antagonistic mechanical balance within the dynein-kinesin microtubular motor system. Dynein activity drives microtubular network inward compaction, while isolated activity of kinesins bundles and expands MTs into giant circular bands that deform the cell cortex into discoids. Furthermore, we show that dyneins recruit MTs to sites of cell adhesion increasing topographic contact guidance of cells, while kinesins antagonize it via retraction of MTs from sites of cell adhesion. Actin-to-microtubules translocation of septin-9 enhances kinesins-MTs interactions, outbalances activity of kinesins over dyneins and induces discoid architecture of cells. These orthogonal mechanisms of MT network reorganization highlight the existence of an intricate mechanical balance between motor activities of kinesins and dyneins that controls cell 3D architecture, mechanics, and cell-microenvironment interactions.

scholarly journals Mechanical Counterbalance of Kinesin and Dynein Motors in a Microtubular Network Regulates Cell Mechanics, 3D Architecture, and Mechanosensing

ACS Nano ◽  
2021 ◽  
Author(s):  
Alexander S. Zhovmer ◽  
Alexis Manning ◽  
Chynna Smith ◽  
James B. Hayes ◽  
Dylan T. Burnette ◽  
...  
Keyword(s):  
Cell Mechanics ◽  
3D Architecture ◽  
Microtubular Network

scholarly journals Mesoscale Dynamics of Spectrin and Acto-Myosin shape Membrane Territories during Mechanoresponse

2019 ◽  
Author(s):  
Andrea Ghisleni ◽  
Camilla Galli ◽  
Pascale Monzo ◽  
Flora Ascione ◽  
Marc-Antoine Fardin ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Adhesion ◽  
Membrane Trafficking ◽  
Cell Mechanics ◽  
Dynamic Interaction ◽  
The Other ◽  
Cell Cortex ◽  
Mesoscale Dynamics ◽  
Spectrin Cytoskeleton ◽  
Dynamic Interplay

AbstractThe spectrin cytoskeleton is a major component of the cell cortex. While ubiquitously expressed, its dynamic interaction with the other cortex components, including the plasma membrane or the acto-myosin cytoskeleton, is poorly understood. Here, we investigated how the spectrin cytoskeleton re-organizes spatially and dynamically under the membrane during changes in cell mechanics. We found spectrin and acto-myosin cytoskeletons to be spatially distinct but cooperating during mechanical challenges, such as cell adhesion and contraction, or compression, stretch and osmolarity fluctuations, creating a cohesive cortex supporting the plasma membrane. Actin territories control protrusions and contractile structures while spectrin territories concentrate in retractile zones and low-actin density/inter-contractile regions, acting as a fence to organize membrane trafficking events. We unveil here the existence of a dynamic interplay between acto-myosin and spectrin cytoskeletons necessary to support a mesoscale organization of the lipid bilayer into spatially-confined cortical territories during cell mechanoresponse.

scholarly journals Complementary mesoscale dynamics of spectrin and acto-myosin shape membrane territories during mechanoresponse

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrea Ghisleni ◽  
Camilla Galli ◽  
Pascale Monzo ◽  
Flora Ascione ◽  
Marc-Antoine Fardin ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Adhesion ◽  
Membrane Trafficking ◽  
Cell Mechanics ◽  
Membrane Skeleton ◽  
The Other ◽  
Cell Cortex ◽  
Dynamic Interactions ◽  
Mesoscale Dynamics ◽  
Dynamic Interplay

Abstract The spectrin-based membrane skeleton is a major component of the cell cortex. While expressed by all metazoans, its dynamic interactions with the other cortex components, including the plasma membrane or the acto-myosin cytoskeleton, are poorly understood. Here, we investigate how spectrin re-organizes spatially and dynamically under the membrane during changes in cell mechanics. We find spectrin and acto-myosin to be spatially distinct but cooperating during mechanical challenges, such as cell adhesion and contraction, or compression, stretch and osmolarity fluctuations, creating a cohesive cortex supporting the plasma membrane. Actin territories control protrusions and contractile structures while spectrin territories concentrate in retractile zones and low-actin density/inter-contractile regions, acting as a fence that organize membrane trafficking events. We unveil here the existence of a dynamic interplay between acto-myosin and spectrin necessary to support a mesoscale organization of the lipid bilayer into spatially-confined cortical territories during cell mechanoresponse.

scholarly journals Organizational metrics of interchromatin speckle factor domains: integrative classifier for stem cell adhesion & lineage signaling

2015 ◽  
Vol 7 (4) ◽  
pp. 435-446 ◽  
Author(s):  
Sebastián L. Vega ◽  
Anandika Dhaliwal ◽  
Varun Arvind ◽  
Parth J. Patel ◽  
Nick R. M. Beijer ◽  
...  
Keyword(s):  
Content Analysis ◽  
Stem Cell ◽  
Cell Adhesion ◽  
Nuclear Protein ◽  
Cell Lineage ◽  
Lineage Commitment ◽  
Cell Microenvironment ◽  
Stem Cell Lineage ◽  
High Content Analysis

Timely classification of stem cell lineage commitment in response to cell–microenvironment interactions using high content analysis of sub-nuclear protein organization.

scholarly journals Protocadherin 7 localizes to the plasma membrane during mitosis and promotes cytokinesis by a palmitoylation-dependent mechanism

2020 ◽  
Author(s):  
Nazlı Ezgi Özkan-Küçük ◽  
Mohammad Haroon Qureshi ◽  
Berfu Nur Yiğit ◽  
Altuğ Kamacıoğlu ◽  
Nima Bavili ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Membrane Trafficking ◽  
Myosin Ii ◽  
Cell Types ◽  
Mitotic Cell ◽  
Cortical Reorganization ◽  
Cell Cortex ◽  
Cleavage Furrow ◽  
Cytoskeleton Organization ◽  
Dependent Mechanism

ABSTRACTSuccessful cell division requires dramatic reorganization of the cell cortex in coordination with actomyosin cytoskeleton organization, membrane trafficking and cell adhesion. Although the contractile actomyosin ring is considered as hallmark of cytokinesis, in some cell types cell adhesion systems have been shown to drive cytokinesis independently from actomyosin function. We previously reported that Protocadherin 7 (PCDH7) localizes to the mitotic cortex which is required for building up the full mitotic rounding pressure. Here, we show that PCDH7 localizes to the mitotic cell cortex and to the cleavage furrow by a palmitoylation-dependent mechanism. At the cleavage furrow, PCDH7 facilitates the activation of myosin II and successful cytokinesis. Strikingly, PCDH7 promotes cytokinesis even when the myosin II contractility and integrin mediated adhesion are blocked. This work describes a palmitoylation-dependent cortical reorganization which promotes cytokinesis under different conditions.

scholarly journals Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0254697
Author(s):  
Anne E. Roehrig ◽  
Kristina Klupsch ◽  
Juan A. Oses-Prieto ◽  
Selim Chaib ◽  
Stephen Henderson ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Molecular Mechanisms ◽  
Hippo Pathway ◽  
Contact Inhibition ◽  
Tumour Suppressor ◽  
Cell Cortex ◽  
Dependent Manner ◽  
A Cell ◽  
Cell Cell ◽  
Paf Complex

The PAF complex (PAFC) coordinates transcription elongation and mRNA processing and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions both at the cell cortex and nucleus and is a key mediator of contact inhibition but the molecular mechanisms remain unclear. In this study we have used affinity proteomics to identify novel Merlin interacting proteins and show that Merlin forms a complex with multiple proteins involved in RNA processing including the PAFC and the CHD1 chromatin remodeller. Tumour-derived inactivating mutations in both Merlin and the CDC73 PAFC subunit mutually disrupt their interaction and growth suppression by Merlin requires CDC73. Merlin interacts with the PAFC in a cell density-dependent manner and we identify a role for FAT cadherins in regulating the Merlin-PAFC interaction. Our results suggest that in addition to its function within the Hippo pathway, Merlin is part of a tumour suppressor network regulated by cell-cell adhesion which coordinates post-initiation steps of the transcription cycle of genes mediating contact inhibition.

scholarly journals Keratin 19 maintains E-cadherin localization at the cell surface and stabilizes cell-cell adhesion of MCF7 cells

2020 ◽  
Author(s):  
Sarah Alsharif ◽  
Pooja Sharma ◽  
Karina Bursch ◽  
Rachel Milliken ◽  
Meagan Collins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Cell Mechanics ◽  
Mcf7 Cells ◽  
Growth And Survival ◽  
Recycling Endosomes ◽  
Keratin 19 ◽  
E Cadherin ◽  
Cell Cell

AbstractA cytoskeletal protein keratin 19 (K19) is highly expressed in breast cancer but its effects on breast cancer cell mechanics are unclear. Using KRT19 knockout (KO) cells and cells where K19 expression was rescued, we found that K19 is required to maintain rounded epithelial-like shape and tight cell-cell adhesion of MCF7 cells. A loss of K19 resulted in a lower level of plakoglobin and internalization of E-cadherin in early and recycling endosomes. Inhibiting internalization restored cell-cell adhesion of KRT19 KO cells, suggesting E-cadherin internalization contributes to defective adhesion. Ultimately, while K19 inhibited cell migration, it was required for cells to form colonies in suspension. Our results suggest that K19 stabilizes E-cadherin complexes at the cell membrane to maintain cell-cell adhesion which inhibits cell migration but provides growth and survival advantages for circulating tumor cells. These findings provide context-dependent roles of K19 during metastasis.

scholarly journals Plasticity of cell migration resulting from mechanochemical coupling

2019 ◽  
Author(s):  
Yuansheng Cao ◽  
Elisabeth Ghabache ◽  
Wouter-Jan Rappel
Keyword(s):  
Cell Mechanics ◽  
Reaction Diffusion ◽  
Cell Cortex ◽  
Actin Network ◽  
Wild Type ◽  
Relaxation Oscillators ◽  
Reaction Diffusion Model ◽  
Mechanochemical Coupling ◽  
Model Predictions ◽  
Signaling Events

AbstractEukaryotic cells can migrate using different modes, ranging from amoeboid-like, during which actin filled protrusions come and go, to keratocyte-like, characterized by a stable morphology and persistent motion. How cells can switch between these modes is still not well understood but waves of signaling events on the cell cortex are thought to play an important role in these transitions. Here we present a simple two component biochemical reaction-diffusion model based on relaxation oscillators and couple this to a model for the mechanics of cell deformations. Different migration modes, including amoeboid-like and keratocyte-like, naturally emerge through phase transitions determined by interactions between biochemical traveling waves, cell mechanics and morphology. The model predictions are explicitly verified by systematically reducing the protrusive force of the actin network in experiments using wild-typeDictyostelium discoideumcells. Our results indicate the importance of coupling signaling events to cell mechanics and morphology and may be applicable in a wide variety of cell motility systems.

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