Speaker: Professor Alexander Bershadsky, Senior Principal Research Scientist, Mechanobiology Institute, National University of Singapore 

Host: Gareth Jones

The cytoskeleton and associated cell adhesions collectively drive cell morphogenesis. In my presentation, two aspects of this topic will be discussed:

Crosstalk between cell-matrix adhesions, microtubules, and actomyosin. Integrin adhesion receptors assemble into various types of actin cytoskeleton-associated structures such as focal adhesions, fibrillar adhesions, and podosomes. These structures are controlled by microtubules via regulation of myosin-IIA-filament assembly. Microtubules are coupled with integrin adhesions via the KANK family of proteins. This coupling controls release of the guanine nucleotide exchange factor GEF-H1 from microtubules, activation of Rho/Rho kinase, and the assembly of myosin IIA filaments, which in turn remodel the adhesions. This mechanism appears to be universal for many cell types.

Emerging left-right asymmetry. Human fibroblasts confined to circular adhesive islands exhibit a chiral actin cytoskeleton swirling,  evolving because of a unidirectional tilting of the radial actin fibers. Analysis of molecular players by knocking down major actin-associated proteins and automated AI-based measurements of radial fiber tilting revealed a group of actin regulators controlling the development of chirality. The cell groups confined to rectangular micropattern demonstrate a chiral cell alignment - an asymmetric tilt of average cell orientation relative to the rectangle long axis. Analysis of about 40 different knockdowns and pharmacological treatments revealed remarkable correlation between their effects on the individual and collective cell chirality. Thus, chiral actin self-organization could underlie the left-right asymmetry seen in tissues and organs.