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Mechanical forces in the immune system

Nature Reviews Immunology volume 17, pages 679–690 (2017)Cite this article

Subjects

Key Points

  • Immune cells lead physically active 'lifestyles' that are characterized by shape change, migration and the formation of dynamic cell–cell interactions.

  • Leukocytes use mechanical cues to adjust their mode of migration to the prevailing environmental conditions.

  • Mechanically induced catch bonds have a crucial role in immune cell trafficking, lymphocyte activation and immunological synapse formation.

  • Lymphocytes use mechanical force to discriminate between high-affinity and low-affinity antigens.

  • Force exertion enables immune cells to control the strength and the specificity of their effector responses.

Abstract

Leukocytes can completely reorganize their cytoskeletal architecture within minutes. This structural plasticity, which facilitates their migration and communicative function, also enables them to exert a substantial amount of mechanical force against the extracellular matrix and the surfaces of interacting cells. In recent years, it has become increasingly clear that these forces have crucial roles in immune cell activation and subsequent effector responses. Here, I review our current understanding of how mechanical force regulates cell-surface receptor activation, cell migration, intracellular signalling and intercellular communication, highlighting the biological ramifications of these effects in various immune cell types.

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Figure 1: Force exertion and mechanotransduction.
Figure 2: Mechanical forces in cell migration.
Figure 3: Mechanical forces in immune cell–cell interactions.

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Acknowledgements

The author thanks L. Kam and S. Grinstein for advice and discussions. This work was supported by the US National Institutes of Health National Institute of Allergy and Infectious Diseases (grant R01AI087644) and the US National Science Foundation (grant CMMI-1562905).

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  1. Immunology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, 10065, New York, USA

    Morgan Huse

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PowerPoint slides

Glossary

Focal adhesions

Force-bearing multiprotein complexes (composed of integrins, cytoskeletal adaptors and signalling molecules) that anchor the cortical filamentous actin cytoskeleton of adherent cells to the extracellular matrix.

Mechanosensing

The capacity of cells or molecules to detect physical properties or perturbations.

Mechanotransduction

The process through which cells sense and respond to their mechanical environment, such as the extracellular matrix, adjacent cells or external stresses. During mechanotransduction, mechanical signals are sensed and activate intracellular biochemical signalling pathways.

Slip bonds

Bonds that are characterized by having a lifetime that decreases with applied force.

Catch bond

A bond that is characterized by having a lifetime that increases up to an optimal applied force, after which it decreases with increasing force.

Lamellipodium

A broad, flat protrusion at the leading edge of a moving cell that is enriched with a branched network of elongating actin filaments that generate the force to push the cell membrane forwards.

Uropod

A slender appendage that is formed at the trailing, rear edge of fast-migrating cells such as amoebae, neutrophils and lymphocytes.

Inside-out signalling

The process by which intracellular signalling mechanisms result in the activation of a cell-surface receptor, such as an integrin. By contrast, outside-in signalling is the process by which the ligation of a cell-surface receptor activates signalling pathways inside the cell.

WASP-family verprolin-homologous protein 2 complex

(WAVE2 complex). A complex that comprises five proteins and that regulates actin-related protein 2/3 (ARP2/3) complex-mediated actin assembly. The defining member of this complex, WAVE, is related to Wiskott–Aldrich syndrome protein and directly stimulates the ARP2/3 complex to nucleate actin assembly, while other components of the complex regulate WAVE.

Extravasate

To move out of the circulatory system, typically through vessel walls. Extravasation is also called diapedesis.

Immunological synapse

A large junctional structure that forms between a lymphocyte and its antigen-presenting cell (APC). The immunological synapse regulates lymphocyte activation, cell adhesion and the directional secretion of cytokines and cytolytic factors.

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Huse, M. Mechanical forces in the immune system. Nat Rev Immunol 17, 679–690 (2017). https://doi.org/10.1038/nri.2017.74

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