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Jakuszeit, T.

Publications and source records attributed to Jakuszeit, T..

4 recordsLinked to original sources

Torque-based immune cell chemotaxis in complex environments

Directed migration in chemical gradients is crucial to the immune response, yet how immune cells navigate complex tissues remains incompletely understood. Using in vitro migration assays and theoretical modeling, we uncover distinct chemotactic strategies in two key immune cell types: neutrophils and dendritic cells (DCs). DCs actively steer toward chemokine gradients via a deterministic torque-like reorientation, while neutrophils bias movement by modulating angular noise and speed. A quantitative Fokker-Planck framework decomposes these behaviors into deterministic and stochastic components. Cytoskeletal perturbations show that microtubules enable torque-based navigation in DCs in collagen gels, whereas actomyosin contractility is required for noise modulation employed by neutrophils and DCs in 2D confined migration assays. Despite both achieving directed migration, the two strategies result in opposing macroscopic outcomes: torque-driven cells minimize dispersion, while noise-biased migration enhances population spread. These results reveal distinct navigation aligned with immune function and demonstrate that immune cell chemotaxis is tuned by cytoskeletal architecture and environmental context.

biophysics↗

Chemokinesis by a microbial predator

Regulated motility is vital for many cells--both for unicellular microbes and for cells within multicellular bodies. Different conditions require different rates and directions of movement. For the microbial predator Capsaspora owczarzaki, its motility is likely essential for predation. This organism has been shown to prey on diverse organisms, including the schistosome parasites that co-reside with it in Biomphalaria glabrata snails. Capsaspora is also an evolutionary model for the unicellular ancestor of animals. This phylogenic placement makes Capsasporas motility an attractive target for understanding the evolution of motility in animal cells. Until now, little was known of how Capsaspora regulates it rate and direction of motility. Here we found that it exhibits chemokinesis (increased movement in response to chemical factors) in response to proteins released from prey cells. Chemokinesis also occurs in response to pure proteins--including bovine serum albumin. We found that this chemokinesis behavior is dependent on Capsaspora cell density, which suggests that the regulated motility is a cooperative behavior (possibly to improve cooperative feeding). We developed a mathematical model of Capsaspora motility and found that chemokinesis alone does not benefit Capsaspora predation. However, when coupled with chemotaxis (directional motility along a chemical gradient toward prey), chemokinesis may improve predation. Finally, we quantitatively analyzed Capsasporas previously reported chemotaxis behavior. These findings lay a foundation for characterizing the mechanisms of regulated motility in a predator of a human pathogen and a model for the ancestor of animals.

biochemistry↗

Fast adaptation of Myosin II activity to confinement sustains neutrophil migration in capillaries

As the first responders of the immune system, neutrophils rapidly and abundantly reach inflamed tissues through blood capillaries. The diameter of capillaries can be as narrow as two microns, imposing considerable deformations on neutrophils. Notably, capillary obstruction due to neutrophil retention causes vascular dysfunction and contributes to the pathogenesis of several diseases. However, the cellular mechanisms that allow neutrophils to migrate into small capillaries and to avoid retention remain unknown. In this study, we demonstrate, both in vivo and in vitro, that capillary size does not influence neutrophil migration velocity. During migration into capillaries of different sizes, neutrophils maintain high speed, a phenomenon associated with a global actomyosin cytoskeleton rearrangement in response to confinement strength. In irregular capillaries, neutrophils rapidly adapt their cell contractility via the ROCK-MyoII pathway, which allows them to sustain their migration speed along the vessels despite changes in confinement. At the single cell level, inhibition of ROCK impairs actomyosin cytoskeleton rearrangement and reduces neutrophil migration speed within confined capillaries. At the collective level, ROCK inhibition hampers efficient neutrophil trafficking in a network of small capillaries, resulting in vessel obstruction. These findings reveal a unique capacity of neutrophils to rapidly and dynamically adapt their migration to the confinement strength of capillaries, an ability that might limit vascular dysfunction during inflammation.

cell biology↗

Cell minor-axis length is a critical feature for breast cancer cell migration on straight, wavy, loop and grid microfibre patterns

Cell migration plays an important role in physiological and pathological processes where the fibrillar morphology of extracellular matrice (ECM) could regulate the migration dynamics. To mimic the morphological characteristics of fibrillar matrix structures, low-voltage continuous electrospinning was adapted to construct straight, wavy, looped and gridded fibre patterns made of polystyrene (of fibre diameter ca. 3 m). With microfibres deposited onto non-passivated surfaces, cells were permitted to explore their different shapes in response to the directly-adhered fibre, as well as to the neighbouring patterns. For all the patterns studied, analysing cellular migration dynamics of MDA-MB-231 (a highly migratory breast cancer cell line) demonstrated a switch in behaviour when the pattern features approach the upper limit of the cell minor axis. Our findings suggest that, although cells dynamically adjust their shapes in response to different fibrillar environments during migration, their ability to divert from an existing fibre track is limited by the size along the cell minor axis. We therefore conclude that the upper limit of cell minor axis might act as a guide for the design of microfibre patterns for different purposes of cell migration.

bioengineering↗