The mechanics of myeloid cells

Abstract

The effects of cell size, shape and deformability on cellular function have long been a topic of interest. Recently, mechanical phenotyping technologies capable of analysing large numbers of cells in real time have become available. This has important implications for biology and medicine, especially haemato-oncology and immunology, as immune cell mechanical phenotyping, immunologic function, and malignant cell transformation are closely linked and potentially exploitable to develop new diagnostics and therapeutics. In this review, we introduce the technologies used to analyse cellular mechanical properties and review emerging findings following the advent of high throughput deformability cytometry. We largely focus on cells from the myeloid lineage, which are derived from the bone marrow and include macrophages, granulocytes and erythrocytes. We highlight advances in mechanical phenotyping of cells in suspension that are revealing novel signatures of human blood diseases and providing new insights into pathogenesis of these diseases. The contributions of mechanical phenotyping of cells in suspension to our understanding of drug mechanisms, identification of novel therapeutics and monitoring of treatment efficacy particularly in instances of haematologic diseases are reviewed, and we suggest emerging topics of study to explore as high throughput deformability cytometers become prevalent in laboratories across the globe.

Obstruction of Capillaries by circulating large Monocytes causes Multi Organ Dysfunction Syndrome (MODS) in Acute Pancreatitis

“…The depletion of these circulating monocytes did not affect the local and systemic pro-in ammatory immune response, but signi cantly ameliorated organ complications. These ndings suggest that the induction of MODS in severe pancreatitis is not mediated by an immunological signalling pathway but related to the physical properties of the monocytes 21 . Lung and kidney are characterised by microvascular systems and the passage of large cells, like monocytes, through these capillary systems requires a exible adaptation to their small capillaries 41 .…”

“…As the monocyte depletion in our mouse model did not alter the local and systemic immune responses we speculated that a cell-mediated effect might be operative in the induction of organ damage. Beside their signalling involvement in immune regulation networks, the mechanical characteristics of myeloid derived cells have been discussed in a pathophysiological context in the recent literature 21 . In further experiments we isolated blood cells from mice and analysed their mechanical properties by real-time uorescence and deformability cytometry (RT-FDC) after gating for 1) Ly6g+/CD11b-neutrophils, 2) Ly6g+/CD11b + gMDSCs and 3) Ly6g-/CD11b + monocytes (Fig.…”

Physical phenotype of blood cells is altered in COVID-19

“…Hyperinflammation and cytokine storm syndrome are reported in COVID-19 cases with high levels of macrophage inflammatory protein 1-α, granulocyte-colony stimulating factor, interleukin (IL)-2, IL-7, interferon-γ inducible protein 10, monocyte chemoattractant protein 1, and tumour necrosis factor-α (49). Such cytokines were reported to induce cytoskeletal changes in myeloid cells and to interfere with their physical phenotypes during immune function (50–52).…”

Dwellers and Trespassers: Mononuclear Phagocytes at the Borders of the Central Nervous System

“…Given a differential expression of interaction molecules and chemokine receptors, monocyte subtypes display intrinsic variance in this multistep process ( 132 ). Cell deformability through cytoskeletal reorganization and membrane stiffness changes are also regulators of trafficking ( 154 ). During trans-endothelial migration, monocytes interact with the endothelial molecules CD99, PECAM1 and CD155 ( 155 ) and, following diapedesis, cross the vascular basement membrane and interact with other perivascular cells ( 144 , 156 ).…”