Mechanics of leukocyte locomotion
|Starts:||13:00 10 May 2016|
|Ends:||14:00 10 May 2016|
|What is it:||Seminar|
|Organiser:||Faculty of Life Sciences|
|Who is it for:||University staff, Current University students|
|Speaker:||Professor Michael Sixt|
The organization principle of the immune system is based on high speed cell motility. Accordingly, immune cells migrate up to 100 times faster than mesenchymal and epithelial cell types. Although the biophysical migration mode of such fast cells is still poorly investigated some principles are emerging and it is now well established that leukocytes do not strictly rely on transmembrane adhesion receptors when they crawl through the interstitial environment, which is usually a 3D scaffold of extracellular matrix molecules. Instead leukocytes are able to directly transduce force by deformations of the cell body. Using in vitro and ex vivo imaging approaches we demonstrate that deformation based migration is not the default strategy of leukocyte locomotion but rather part of a plasticity program that allows the cells to instantaneously switch between adhesion receptor dependent and independent migration. We find that invasion of dense matrices and crawling over stiff surfaces relies on adhesion while migration in the confined space of an interstitium does not and that leukocyte can shift back and forth between these modes without altering their proteome. Apart from the geometry of the extracellular environment also the distribution of the guidance cue can dictate the locomotion strategy and immobilized cues preferentially cause adhesive migration whereas soluble cues trigger adhesion independent movement.
The force generating module of leukocytes is exclusively based on actomyosin protrusions and contractions. But also here the cells show enormous plasticity and we found that blocking contractility shifts the cells towards a entirely protrusive lomomotion strategy, while dampening protrusion activates the blebbing mode. When interfering with actin nucleators we found that ablation of Arp2/3 activity at the leading edge abrogated branching and shifted the cells towards a linearly elongated cell shape. However, this did not slow down locomotion, but merely prevented the cells from turning and responsing to directional cues, while actual speed was accelerated.
Professor Michael Sixt
Organisation: Institute of Science & Technology
Travel and Contact Information
Michael Smith Lecture Theatre
Michael Smith Building