Mechanobiology of Neutrophil Durotaxis: How the Centrosome and Microtubules Regulate Nuclear Mechanics in Confined Neutrophil Durotaxis

• Applicant: Dr. Fatemeh Abbasi, Ph.D.
• Subject Area: Cell Biology ; Biophysics
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 584722918

Neutrophils are the most abundant and fastest migrating immune cells, enabling rapid defense against pathogens in tissues that differ widely in mechanical stiffness. During their journey from the bone marrow to sites of infection, they must cross steep stiffness gradients (a process known as durotaxis) and move under strong mechanical confinement. Such physical challenges require precise coordination of traction-force generation and mechanical adaptation. A distinctive feature of neutrophils is their multilobulated nucleus, which confers exceptional deformability and allows passage through constrictions smaller than the cell itself. However, the physical principles by which nuclear architecture and cytoskeletal organization jointly control force transmission and stiffness-guided migration remain poorly understood. Using Confinement Force Microscopy (CFM), a method I developed to quantify three-dimensional traction forces during live imaging, I found that neutrophils undergo robust 3D durotaxis under confinement. When switching from soft to stiff substrates, they exhibit a transient traction-stress redistribution, indicating that stiffness detection is an active, mechanically regulated process rather than a purely adhesion response. In this project, I will investigate how the centrosome and microtubule cytoskeleton regulate neutrophil durotaxis under geometric confinement and how they contribute to maintaining nuclear integrity during this process. I hypothesize that centrosome positioning and microtubule organization act as central mechanical regulators that tune nuclear deformation and traction-force balance during durotaxis. The project will combine CFM-based force mapping, stiffness-controlled confinement, and live imaging of centrosomes, microtubules, and nuclei to dissect these processes quantitatively. By linking organelle positioning to mechanical output, this work will uncover fundamental principles of cellular mechano-sensing, traction force coordination, and adaptive stress regulation in amoeboid-migrating immune cells. Beyond advancing biophysical understanding of neutrophil migration, the results will provide a general framework for how cells translate mechanical cues into functional behavior across diverse physiological contexts.

• DFG Programme: Position