Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Poster Abstracts

20-POS Board 20 Harnessing Actomyosin Nucleators and Regulators to Control T Cell Migration Jorge L. Galeano-Niño 1 , Weimiao Yu 2 , Szun S. Tay 1 , Adam J. Cook 3 , Maté Biro 1,3 . 1 EMBL Australia Node in Single Molecule Science, Sydney, NSW, Australia, 2 Institute of Molecular and Cell Biology (IMCB), Singapore, Singapore, 3 The University of Sydney, Sydney, NSW, Australia. The main immune cells responsible for antitumor activity are Cytotoxic T cells (CTLs). They constitutively patrol organs for cognate antigen and typically migrate using an elongated and polarised shape with a dynamic leading edge and a uropod at the rear. T cells are however able to adopt diverse migration modes depending on both extra- and intracellular cues. The actomyosin cytoskeleton is responsible for the mechanical forces that are involved in the migratory process. The polymerisation of actin filaments, mediated by Arp2/3 complex or formins (actin nucleators), and the contractility of myosin motor proteins, collectively determine the morphology and underpin the migration of cells. However, their functionality during T cell migration remains incompletely understood. Using 3-dimensional migration assays and novel image analysis methods, we found that inhibiting specific components of the actomyosin cortex, CTLs can be forced to adopt different migration modes and extend distinct sets of protrusions. The pharmacological inhibition of formins induces a loss of directionality during CTL scanning. These finding suggest that formins are required for directional maintenance by CTLs and thus their overall scanning efficiency. The inhibition of particular actomyosin nucleators or regulators modifies the migration T cells in a predictable and specific manner, and could thus open up novel therapeutic avenues for controlling both excessive and deficient T cell movement in various pathological contexts ranging from autoimmune diseases to cancers.

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