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The cytoskeleton is a complex network of interconnected biopolymers consisting of actin filaments, microtubules, and intermediate filaments. These biopolymers work in concert to transmit cell-generated forces to the extracellular matrix required for cell motility, wound healing, and tissue maintenance. While we know cell-generated forces are driven by actomyosin contractility and balanced by microtubule network resistance, the effect of intermediate filaments on cellular forces is unclear. Using a combination of theoretical modeling and experiments, we show that vimentin intermediate filaments tune cell stress by assisting in both actomyosin-based force transmission and reinforcement of microtubule networks under compression. We show that the competition between these two opposing effects of vimentin is regulated by the microenvironment stiffness. These results reconcile seemingly contradictory results in the literature and provide a unified description of vimentin’s effects on the transmission of cell contractile forces to the extracellular matrix.
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Subcellular context-specific tuning of actomyosin ring contractility within a common cytoplasm
Summary The non-muscle actomyosin cytoskeleton generates contractile force through the dynamic rearrangement of its constituent parts. Actomyosin rings are a specialization of the non-muscle actomyosin cytoskeleton that drive cell shape changes during division, wound healing, and other events. Contractile rings throughout phylogeny and in a range of cellular contexts are built from conserved components including non-muscle myosin II (NMMII), actin filaments (F-actin), and crosslinking proteins. However, it is unknown whether diverse actomyosin rings close via a single unifying mechanism. To explore how contractile forces are generated by actomyosin rings, we studied three instances of ring closure within the common cytoplasm of theC. elegansoogenic germline: mitotic cytokinesis of germline stem cells (GSCs), apoptosis of meiotic compartments, and cellularization of oocytes. We found that each ring type closed with unique kinetics, protein density and abundance dynamics. These measurements suggested that the mechanism of contractile force generation varied across the subcellular contexts. Next, we formulated a physical model that related the forces generated by filament-filament interactions to the material properties of these rings that dictate the kinetics of their closure. Using this framework, we related the density of conserved cytoskeletal proteins anillin and NMMII to the kinematics of ring closure. We fitted model rings to in situ measurements to estimate parameters that are currently experimentally inaccessible, such as the asymmetric distribution of protein along the length of F-actin, which occurs naturally due to differences in the dimensions of the crosslinker and NMMII filaments. Our work predicted that the role of NMMII varies across these ring types, due in part to its distribution along F-actin and motoring. Our model also predicted that the degree of contractility and the impact of ring material properties on contractility differs among ring types.
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- Award ID(s):
- 2153790
- PAR ID:
- 10577406
- Publisher / Repository:
- bioRxiv
- Date Published:
- Format(s):
- Medium: X
- Institution:
- bioRxiv
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Posted Content:
- https://doi.org/10.1101/2024.08.08.607200
