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Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.
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A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
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Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
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Evaluation of Cancer Stem Cell Migration Using Compartmentalizing Microfluidic Devices and Live Cell Imaging
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T cell morphodynamics reveal periodic shape oscillations in three-dimensional migration.

Henry Cavanagh1, Daryan Kempe2, Jessica K Mazalo2

  • 1Imperial College London, Centre for Integrative Systems Biology and Bioinformatics, London SW7 2BU, UK.

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|May 10, 2022
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Summary

T cells exhibit complex shape changes during migration, with distinct run-and-stop behaviors identified. These morphodynamic patterns, analyzed in 3D, reveal periodic oscillations crucial for cell movement and immune response.

Keywords:
T cellslattice light-sheet microscopemorphodynamicsphysics of behaviourshape analysis

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Area of Science:

  • Immunology
  • Cell Biology
  • Biophysics

Background:

  • T cell migration is vital for immune surveillance and response against pathogens and cancer.
  • Quantitative understanding of T cell morphodynamics in 3D extracellular matrices (ECMs) and over time is limited.

Purpose of the Study:

  • To quantitatively explore the 3D morphodynamics of migrating T cells at high spatio-temporal resolution.
  • To develop novel methods for analyzing T cell shape dynamics and migration behaviors.

Main Methods:

  • Utilized advanced lattice light-sheet microscopy for high-resolution imaging.
  • Developed a novel shape descriptor using spherical harmonics, including uropod polarization.
  • Applied multiscale wavelet analysis to map morphodynamic composition of migration modes.

Main Results:

  • Identified a low-dimensional shape space for T cells.
  • Characterized 'run-and-stop' migration modes emerging around 150 seconds.
  • Discovered periodic (approx. 100s) biphasic morphodynamic oscillations during the 'run' mode, involving front-widening, uropod retraction, and rearward/forward motion.

Conclusions:

  • T cell migration involves stereotyped morphodynamic motifs within distinct behavioral modes.
  • Periodic oscillations and ECM intercalation are key to T cell forward motion.
  • These findings can inform comparisons across different T cell conditions and enhance immunotherapies.