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Actin networks in super resolution

École polytechnique’s Laboratory for Optics and Biosciences (LOB) participated in a study coordinated by the Institute of Biology Paris-Seine on the discovery of a cellular mechanism essential to embryonic development that has just been published in Nature.

réseaux d'actine en super résolution obtenue au LOB

The Caenorhabditis elegans worm (C. elegans) is a particularly interesting model organism for the study of morphogenesis, the processes that determine the shape and structure of tissues, organs, and organisms.

During embryonic development, the C. elegans is elongated to twice its length as a result of muscle contractions that deform the epidermis. This process seems counter-intuitive given that muscles usually go back to their initial shape after contracting.

From this behavior, researchers at the Institute of Biology Paris-Seine Laboratory of Biological Development (IBPS, CNRS/Sorbonne Université) postulated the existence of a mechanism that stabilizes the embryo’s transient cell shapes following each muscle contraction.

They developed a multidisciplinary experimental method to verify this hypothesis, combining genetics, cellular biology and physics.

The study identified the molecular nature of the mechanism. Starting from the protein kinase, known for regulating certain mechanical properties of cells, the researchers identified a new partner constitutive of the cell’s skeleton: alpha-spectrin. They demonstrated that the combined absence of these two factors caused the C. elegans embryo to retract after muscle contractions.

Using genetic approaches and high-resolution imaging at the LOB, they established that these two proteins orchestrate the remodeling of the actin cytoskeleton (the intracellular network that gives the cell its stiffness and elasticity) of the epidermis with the help of proteins that sever and then bundle the actin filaments.

The super-resolution optical imagery produced using one of the systems of the Morphoscope platform evidenced differences in microstructure between a well-shaped cytoskeleton and a disorganized cytoskeleton where the actin filaments are not parallel.

The findings suggest that these proteins control the remodeling of the actin network and enable the blocking of the shape of the cell in a process with a ratchet-like mechanism and they underscore the importance of elasticity in the modification of the shape of cells.

These discoveries may have implications for our understanding of the morphogenesis of organs in contact with epithelial tissue, wound healing processes, or the invasive character of tumor cells. Because our organs are organized with contractile cells juxtaposed with epithelial cells, the latter are very regularly subjected to mechanical forces that can modify their shape, behavior, or function. Several diseases, including some forms of cancer, are due to a poor response to mechanical stress.

Find out more :

An actin-based viscoplastic lock ensures progressive body axis elongation

Alicia Lardennois, Gabriella Pásti, Teresa Ferraro, Flora Llense, Pierre Mahou, Julien Pontabry, David Rodriguez, Samantha Kim, Shoichiro Ono, Emmanuel Beaurepaire, Christelle Gally, Michel Labouesse

Nature, 28 août 2019

https://doi.org/10.1038/s41586-019-1509-4