Format

Send to

Choose Destination
Biochim Biophys Acta Mol Cell Res. 2019 Jul 23. pii: S0167-4889(19)30125-9. doi: 10.1016/j.bbamcr.2019.07.011. [Epub ahead of print]

Cell spread area and traction forces determine myosin-II-based cortex thickness regulation.

Author information

1
Dept. of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, West Bengal, India.
2
Dept. of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, West Bengal, India. Electronic address: bidisha.sinha@iiserkol.ac.in.

Abstract

Actomyosin network under the plasma membrane of cells forms a cortical layer that regulates cellular deformations during different processes. What regulates the cortex? Characterized by its thickness, it is believed to be regulated by actin dynamics, filament-length regulators and myosin motor proteins. However, its regulation by cellular morphology (e.g. cell spread area) or mechanical microenvironment (e.g. substrate stiffness) has remained largely unexplored. In this study, super- and high-resolution imaging of actin in CHO cells demonstrates that at high spread areas (>450 μm2), the cortex is thinner, better separated as layers, and sensitive to deactivation of myosin II motors or reduction of substrate stiffness (and traction forces). In less spread cells (<400 μm2) such perturbations do not elicit a response. Myosin IIA's mechanosensing is limited here due to its lowered actin-bound fraction and higher turnover rate. Cofilin, in line with its competitive inhibitory role, is found to be overexpressed in these cells. To establish the causal relation, we initiate a spread area drop by de-adhesion and find enhanced actin dynamics and fragmentation along with oscillations and increase in thickness. This is more correlated to the reduction of traction forces than the endocytosis-based reduction in cell volume. Cortex thickness control by spread area is also found be true during differentiation of THP-1 monocytes to macrophages. Thus, we propose that spread area regulates cortex and its thickness by traction-based mechanosensing of myosin II.

KEYWORDS:

Actin cortex; Cell spread area; Cortex thickness; Myosin II; Super-resolution imaging; Traction forces

PMID:
31348954
DOI:
10.1016/j.bbamcr.2019.07.011
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center