Research Topic

 

Cell migration is a universal feature of all metazoan life and crucially involved in most developmental, homeostatic and pathological processes. Efforts to understand its molecular and mechanical aspects are largely focused on the “haptokinetic” paradigm. Here cells generate traction by coupling the protrusive and contractile forces of the actomyosin cytoskeleton via transmembrane receptors to the extracellular environment. Our recent work demonstrated that leukocytes, the class of animal cells that migrates with highest speed and efficiency, violate this paradigm. Once embedded in physiological three-dimensional matrices they instantaneously shift between adhesive and non-adhesive modes to transduce forces. We use a combined cell biological and biophysical approach to elucidate the molecular and mechanical principles underlying such plasticity. We currently focus on the machinery most proximate to force generation and use genetics and pharmacology to characterize how nucleation, elongation, depolymerization and crosslinking of actin filaments act in leukocytes migrating through environments of varying geometry and adhesive properties. We employ advanced live cell fluorescence imaging in combination with artificial environments engineered using microfluidics and substrate micropatterning. In addition we develop new cellular tools to allow better genetic manipulation of leukocytes.

 

 

 

Team Members

Michael Sixt, PI

Eva Kiermaier, Postdoc

Anne Reversat, Postdoc

Ingrid de Vries, Senior Technician