Traditionally, cell migration has been studied on two-dimensional (2D) surfaces, where cells generate traction by coupling the forces of the actin cytoskeleton to the extracellular environment via integrin transmembrane receptors. However, observations in three-dimensional (3D) environments reveal that 2D overemphasizes adhesion and integrin-requirement. Leukocytes such as dendritic cells are especially independent of integrins: in vivo the interstitial motility of integrin-deficient leukocytes is indistinguishable from their wild-type counterparts (Lämmermann et al., 2008).
The aim of my main project is to decipher how leukocytes can move into complex environment without adhesion-based force coupling of the actin cytoskeleton. To rule out adhesion in leukocyte I created talin-deficient leukocytes using the Cas9/CRISPR genome editing system (Zhang lab). In addition, I set-up a PDMS device (Le Berre et al., 2014) that allows for real time microscopy combined with variable degrees of confinement between 2 parallel surfaces (2,5D), and I also increased the complexity of this environment by adding different topographical irregularities.


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