Unraveling the mechanobiology of immune cells

Zhang, Xuexiang; Kim, Tae-Hyung; Thauland, Timothy J.; Li, Hongjun; Majedi, Fatemeh Sadat; Ly, Chau; Gu, Zhen; Butte, Manish J.; Rowat, Amy C.; Li, Song

doi:10.1016/j.copbio.2020.09.004

Cited by 64 publications

(42 citation statements)

References 64 publications

(107 reference statements)

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“…Thus, a universal property of immune cells is their capacity to exit the circulation and to enter tissues (Fig 5 ). The ability to sense and respond to mechanical cues is essential for the development, activation, differentiation and expansion of immune cells (Zhang et al , 2020 ). In the blood, immune cells are subjected to the flow forces generated by the heartbeat, which gives rise to blood pressure.…”

Section: Mechanical Stress Protection In the Immune Systemmentioning

confidence: 99%

Maintaining proteostasis under mechanical stress

et al. 2021

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Cell survival, tissue integrity and organismal health depend on the ability to maintain functional protein networks even under conditions that threaten protein integrity. Protection against such stress conditions involves the adaptation of folding and degradation machineries, which help to preserve the protein network by facilitating the refolding or disposal of damaged proteins. In multicellular organisms, cells are permanently exposed to stress resulting from mechanical forces. Yet, for long time mechanical stress was not recognized as a primary stressor that perturbs protein structure and threatens proteome integrity. The identification and characterization of protein folding and degradation systems, which handle force‐unfolded proteins, marks a turning point in this regard. It has become apparent that mechanical stress protection operates during cell differentiation, adhesion and migration and is essential for maintaining tissues such as skeletal muscle, heart and kidney as well as the immune system. Here, we provide an overview of recent advances in our understanding of mechanical stress protection.

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Section: Mechanical Stress Protection In the Immune Systemmentioning

confidence: 99%

Maintaining proteostasis under mechanical stress

et al. 2021

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“…The interplay between these different modalities is still unexplored. In addition to long range mechanical interactions, cells may sense other cells by short-range mechanosensation and adhesion mechanisms, including ligand based bond interactions, by biochemical signalling and other molecular recognition mechanisms [ 22 ], by haptotaxis [ 23 ], as well as by responses to specific molecules or signals put forth by neighboring cells [ 25 , 27 ]. A salient example is that of immune cells that can sense and respond to biophysical cues—from dynamic forces to spatial features—during their development, activation, differentiation, and expansion, as well as to biochemical cues.…”

Section: Discussion and Future Extensions To Other Forms Of Interactionsmentioning

confidence: 99%

“…In this context, it is useful to compare non-contact and long range mechanical signalling, as analyzed by these studies, to cell–cell interactions that are not mechanical; specifically, chemical signalling, such as in immune cell interactions (for instance, see the review by [ 22 ] and references therein), or other forms of interactions, such as haptotaxis [ 23 , 24 , 25 , 26 , 27 , 28 ], cell stimulation by activating or secretory molecules, such as in inflammation and thromboses [ 29 , 30 ]. Mechanical non-local interactions between cells offer advantages as compared to chemical means in terms of the rate at which cells can communicate.…”

Section: Introductionmentioning

confidence: 99%

Matrix Stiffness Modulates Mechanical Interactions and Promotes Contact between Motile Cells

2021

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The mechanical micro-environment of cells and tissues influences key aspects of cell structure and function, including cell motility. For proper tissue development, cells need to migrate, interact, and form contacts. Cells are known to exert contractile forces on underlying soft substrates and sense deformations in them. Here, we propose and analyze a minimal biophysical model for cell migration and long-range cell–cell interactions through mutual mechanical deformations of the substrate. We compute key metrics of cell motile behavior, such as the number of cell-cell contacts over a given time, the dispersion of cell trajectories, and the probability of permanent cell contact, and analyze how these depend on a cell motility parameter and substrate stiffness. Our results elucidate how cells may sense each other mechanically and generate coordinated movements and provide an extensible framework to further address both mechanical and short-range biophysical interactions.

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“…This mechanism mediated by the cytoskeleton that serves as a global mechanosensor apparatus, permits cells to sense their extracellular environment and rapidly respond to different stimuli. NK cell mechanosensors include a large range of activating receptors as well as b1 and b2 integrins and CD62L selectin (9,10).The actomyosin network plays an important role in mechanotransduction, in that actin polymerization generates a "pushing" force, whereas the myosin produces a "pulling" force, and together are translated into several signaling cascades (11,12). Thus, the actin cytoskeleton provides the mechanical forces necessary for adhesion, migration and tissue infiltration of NK cells as well as for their cytotoxic function.…”

Section: Mechanosensing In the Nk Cell-mediated Immune Responsesmentioning

confidence: 99%

Mechanosensation and Mechanotransduction in Natural Killer Cells

et al. 2021

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Natural killer (NK) cells are a main subset of innate lymphocytes that contribute to host immune protection against viruses and tumors by mediating target cell killing and secreting a wide array of cytokines. Their functions are finely regulated by a balance between activating and inhibitory receptors and involve also adhesive interactions. Mechanotransduction is the process in which physical forces sensed by mechanosensors are translated into chemical signaling. Herein, we report findings on the involvement of this mechanism that is mainly mediated by actin cytoskeleton, in the regulation of NK cell adhesion, migration, tissue infiltration and functions. Actin represents the structural basis for NK cell immunological synapse (NKIS) and polarization of secretory apparatus. NK-target cell interaction involves the formation of both uropods and membrane nanotubes that allow target cell interaction over long distances. Actin retrograde flow (ARF) regulates NK cell signaling and controls the equilibrium between activation versus inhibition. Activating NKIS is associated with rapid lamellipodial ARF, whereas lower centripetal actin flow is present during inhibitory NKIS where β actin can associate with the tyrosine phosphatase SHP-1. Overall, a better knowledge of mechanotransduction might represent a future challenge: Realization of nanomaterials tailored for NK cells, would be important to translate in vitro studies in in vivo new immunotherapeutic approaches.

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Unraveling the mechanobiology of immune cells

Cited by 64 publications

References 64 publications

Maintaining proteostasis under mechanical stress

Maintaining proteostasis under mechanical stress

Matrix Stiffness Modulates Mechanical Interactions and Promotes Contact between Motile Cells

Mechanosensation and Mechanotransduction in Natural Killer Cells

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