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Mechanobiology of Disease
Poster Abstracts
78
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.