Biophysical Society Thematic Meeting

Mechanobiology of Disease

Thursday Speaker Abstracts

Cortex Architecture Regulates Cortex Tension during the Cell Cycle

Priyamvada Chugh

, Andrew G. Clark

1,2

, Matthew B. Smith

, Davide A. Cassani

, Guillaume

Charras

, Guillaume Salbreux

, Ewa K. Paluch

Institut Curie, Paris, France,

MRC-LMCB, University College London, London, United

Kingdom,

The Francis Crick Institute, London, United Kingdom.

London Centre for

Nanotechnology, University College London, London, United Kingdom,

Cell shape regulation is key to a number of fundamental biological processes, including cell

migration and division. In animal cells, cell morphology is controlled primarily by the cortex, a

thin actomyosin network underlying the plasma membrane. The cortex determines global

physical properties of the cell, such as tension. Previous studies have shown that spatial and

temporal changes in cortical tension drive shape changes during the cell cycle, such as mitotic

rounding and cytokinetic furrow ingression. However, the changes in cortical architecture and

composition driving changes in cortical tension remain unclear. We are investigating this

question using a combination of cell biology experiments, quantitative imaging and modeling.

As the cortex dimensions are below the resolution limit of conventional light microscopy, we

have developed a dual-color localization method to investigate the spatial organization of the

cortex. This method is based on estimating the relative localization of cortex components with

respect to one another by labeling them with chromatically different fluorophores. Using our

method, we quantified cortex thickness and compared the localization of key actin binding

proteins in interphase and mitosis. We showed that cortex thickness decreases in mitosis,

indicating a reorganization of the cortical network. Using targeted siRNA knockdowns, we

identified key regulators of cortex thickness. Interestingly, proteins controlling cortex thickness

also affect cortical tension, measured using atomic force microscopy. Agent based simulations of

the cortex shed light on how network spatial organization controls cortex tension. Our systematic

analysis will help uncover the mechanisms by which cortical structure and organization regulate

cortical mechanics, thereby driving cellular morphogenesis.