Imaging and Defining Emergent Behaviors of the Immune Response

T cell Motility

Actin and Myosin Dynamics in Cell Motility:

T cells are motile via at least two distinct mechanisms. The first, which we term ‘Sliding’ is very similar to how mesenchymal cells move on glass or coated surfaces and involves a single contact which translates continuously, akin to a tank tread. The second, involves coordinated placements of one or more contacts onto the substrate in sequence, akin to how humans translate weight between alternating legs, transferring force to the floor to move forward (thus ‘Walking’). We believe the ‘Walking’ mode is more likely the physiological reality in vivo, excepting when integrin levels are really high or, when an intracellular motor protein called myosinIIA is deactivated, for example during TCR signaling. Walking is a faster mode than Sliding whereas the latter, with increased surface contact, is likely to give rise to greater and more prolonged surface contact, which we believe to be important to increase sensitivity to ligands in the environment.

Our lab has studied the cytoskeletal underpinnings of T cell motility since the lab’s inception.  Beyond published works describing roles for myosin and septin molecules in discrete aspect of the movement of these cells, we have used cells deficient in myosin 1g to study how efficient movement leads to efficient surveillance.  This study, published in Cell, showed the important result that merely moving faster did not result in greater efficient surveillance—Myo1g cells appeared to cover more ground but their greater speed effectively limited their ability to effectively detect their targets since they were less intensive in searching any one area.

 

Migratory behavior of fluorescently labeled wild-type (green) and Myo1g/ OT-I (red) cells inside wild-type lymph nodes (LN). The movie cycles through first exploring the volume, showing that these cells occupy the same physical space within the LN. The movie then plays and then each cell phenotype is separately tracked and then tracked together. Tracks are color-coded according to the mean track speed. Scale bar represents 50 microns.

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