Mechanical deformation induces depolarization of neutrophils

Ekpenyong, Andrew; Toepfner, Nicole; Fiddler, Christine; Herbig, Maik; Li, Wenhong; Cojoc, Gheorghe; Summers, Charlotte; Guck, Jochen; Chilvers, Edwin R.

doi:10.1126/sciadv.1602536

Cited by 82 publications

(108 citation statements)

References 60 publications

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“…The physiological benefits of having the lungs as a site of depriming have already been postulated (56,77) and the consequences for pathology hypothesized (16,103). In fact, contemporaneous with our unpublished data showing that mechanical deformation can deprime soluble agonist-activated neutrophils (14) there is emerging clinical evidence that the healthy human lungs selectively retains primed neutrophils in order to deprime them and rerelease them into the systemic circulation as resting cells (104). This recent work suggested that the yet-to-be-identified physiological depriming mechanism(s) may fail in patients with ARDS, resulting in increased numbers of primed neutrophils within the systemic circulation (104).…”

Section: Priming and Depriming By Other Mechanical Stimuli (Constrictsupporting

confidence: 71%

“…Moreover, mechanical stimuli can prime and activate neutrophils. Deformation in narrow channels led to activation and pseudopod formation (14,53), contactless stretching by optical forces yielded similar results (14).…”

Section: Neutrophil States: Resting Versus Activatedmentioning

confidence: 58%

“…Neutrophils exhibit dramatic morphological changes in response to chemical or mechanical stimuli (14,53,59), (see Fig. 1).…”

Section: Morphometry and Response To Mechanical Stimulimentioning

confidence: 99%

“…In Fig. 2, we give the timeline of neutrophil mechanotransduction, from the earliest report of PMN activation by mechanical stress (59), to the recent discovery of depriming of neutrophils by in-vivo-like stretching (14). The physiological and pathophysiological implications of these findings will form the center of our discussion and their clinical relevance will be used to motivate further work in the concluding remarks.…”

Section: Neutrophil Mechanical Properties and Mechanotransductionmentioning

confidence: 99%

“…A major finding, that soluble agonist-activated or primed neutrophils are stiffer than resting neutrophils (14,42,73,118,119) and that such stiffening is a necessary and sufficient condition for sequestration in capillaries (42) has been challenged recently (47,81). Gossett et al imposed very high strains on the cells in their version of the deformability cytometer (81) (DC) and found agonist-activated PMNs to be more deformable than resting PMNs.…”

Section: Morphometric and Rheological Controversiesmentioning

confidence: 99%

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Mechanotransduction in neutrophil activation and deactivation

Ekpenyong

Toepfner

Chilvers

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Mechanotransduction refers to the processes through which cells sense mechanical stimuli by converting them to biochemical signals and, thus, eliciting specific cellular responses. Cells sense mechanical stimuli from their 3D environment, including the extracellular matrix, neighboring cells and other mechanical forces. Incidentally, the emerging concept of mechanical homeostasis,long term or chronic regulation of mechanical properties, seems to apply to neutrophils in a peculiar manner, owing to neutrophils' ability to dynamically switch between the activated/primed and deactivated/deprimed states. While neutrophil activation has been known for over a century, its deactivation is a relatively recent discovery. Even more intriguing is the reversibility of neutrophil activation and deactivation. We review and critically evaluate recent findings that suggest physiological roles for neutrophil activation and deactivation and discuss possible mechanisms by which mechanical stimuli can drive the oscillation of neutrophils between the activated and resting states. We highlight several molecules that have been identified in neutrophil mechanotransduction, including cell adhesion and transmembrane receptors, cytoskeletal and ion channel molecules. The physiological and pathophysiological implications of such mechanically induced signal transduction in neutrophils are highlighted as a basis for future work. This article is part of a Special Issue entitled: Mechanobiology.

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Section: Priming and Depriming By Other Mechanical Stimuli (Constrictsupporting

confidence: 71%

Section: Neutrophil States: Resting Versus Activatedmentioning

confidence: 58%

“…Neutrophils exhibit dramatic morphological changes in response to chemical or mechanical stimuli (14,53,59), (see Fig. 1).…”

Section: Morphometry and Response To Mechanical Stimulimentioning

confidence: 99%

Section: Neutrophil Mechanical Properties and Mechanotransductionmentioning

confidence: 99%

Section: Morphometric and Rheological Controversiesmentioning

confidence: 99%

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Mechanotransduction in neutrophil activation and deactivation

Ekpenyong

Toepfner

Chilvers

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Microsystems for Single‐Cell Analysis

2017

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Due to the heterogeneity that exists even between cells of the same tissue, it is essential to use techniques and devices able to resolve the characteristics of single biological cells, such as morphology, metabolism, or response to drugs. To that end, different structures with sizes similar to that of individual cells have been developed in recent years, which allow single‐cell studies with high sensitivity and high resolution. By employing a variety of sensing strategies, one can obtain complementary information about individual cells, and thus create a complete picture of cellular properties. This review aims to provide an overview of microscale single‐cell sensors. The progress in micrometer‐sized sensing probes as well as microfluidic and micropatterned devices is described, showing the capabilities of the available systems. In addition, a comprehensive compendium of systems based on rolled‐up microtubes, which have the potential to advance and improve the single‐cell analysis microsystem field, is comprised.

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Spheroid Culture of Mesenchymal Stromal Cells Results in Morphorheological Properties Appropriate for Improved Microcirculation

et al. 2019

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Human bone marrow mesenchymal stromal cells (MSCs) are used in clinical trials for the treatment of systemic inflammatory diseases due to their regenerative and immunomodulatory properties. However, intravenous administration of MSCs is hampered by cell trapping within the pulmonary capillary networks. Here, it is hypothesized that traditional 2D plastic‐adherent cell expansion fails to result in appropriate morphorheological properties required for successful cell circulation. To address this issue, a method to culture MSCs in nonadherent 3D spheroids (mesenspheres) is adapted. The biological properties of mesensphere‐cultured MSCs remain identical to conventional 2D cultures. However, morphorheological analyses reveal a smaller size and lower stiffness of mesensphere‐derived MSCs compared to plastic‐adherent MSCs, measured using real‐time deformability cytometry and atomic force microscopy. These properties result in an increased ability to pass through microconstrictions in an ex vivo microcirculation assay. This ability is confirmed in vivo by comparison of cell accumulation in various organ capillary networks after intravenous injection of both types of MSCs in mouse. The findings generally identify cellular morphorheological properties as attractive targets for improving microcirculation and specifically suggest mesensphere culture as a promising approach for optimized MSC‐based therapies.

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Mechanical deformation induces depolarization of neutrophils

Abstract: In vivo–mimicking mechanical deformations quickly depolarize neutrophils—a mechanism potentially failing in acute lung injury.

Cited by 82 publications

References 60 publications

Mechanotransduction in neutrophil activation and deactivation

Mechanotransduction in neutrophil activation and deactivation

Microsystems for Single‐Cell Analysis

Spheroid Culture of Mesenchymal Stromal Cells Results in Morphorheological Properties Appropriate for Improved Microcirculation

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