Single-cell analysis reveals chemokine-mediated differential regulation of monocyte mechanics

Abstract

Summary Monocytes continuously adapt their shapes for proper circulation and elicitation of effective immune responses. Although these functions depend on the cell mechanical properties, the mechanical behavior of monocytes is still poorly understood and accurate physiologically relevant data on basic mechanical properties are lacking almost entirely. By combining several complementary single-cell force spectroscopy techniques, we report that the mechanical properties of human monocyte are strain-rate dependent, and that chemokines can induce alterations in viscoelastic behavior. In addition, our findings indicate that human monocytes are heterogeneous mechanically and this heterogeneity is regulated by chemokine CCL2. The technology presented here can be readily used to reveal mechanical complexity of the blood cell population in disease conditions, where viscoelastic properties may serve as physical biomarkers for disease progression and response to therapy.

Cytosolic Interactome Protects Against Protein Unfolding in a Single Molecule Experiment

“…We compared the viscosity of cytosol solution (indicated as cytosol* in the figure) and buffer ( Figure 1 A) by Acoustic Force Spectroscopy (AFS). [ 25 ] We measured the viscosity by extracting the limit velocity of free‐falling 4 µm silica beads in cytosol solution and buffer, from a starting position determined by the acoustic node generated by the AFS. From the boxplot in Figure 1A, we can observe the spread of the viscosity distribution measured in the two media: buffer viscosity has mean = 9.3 × 10 −4 and standard deviation = 0.6 × 10 −4 Pa s, while the cytosol solution scores a mean of 9.6 × 10 −4 and standard deviation of 0.7 × 10 −4 Pa s. The two distributions compare with a p ‐value of 0.057, as calculated by Kolmogorov test (two‐tailed).…”

Single‐Cell Mechanical Characterization of Human Macrophages

“…Recently, we uncovered the importance of monocyte mechanics in their recruitment to sites of infection, by observing that exposure to CCL2-a chemokine and primary mediator in monocyte recruitment-can increase monocyte stiffness and viscous properties, helping them switch to a migration-competent state and progress to sites of infection. [28] Similarly, in this study, we found that the more migration-competent cells, the M2 macrophages, exhibit increased stiffness as well as viscous properties. This knowledge could, ultimately, provide a novel biomarker for health and disease.…”

Potential Role of LYN, CCL2, ITGB3 and IL6 Genes in the Immune Response of Porcine Buccal Mucosa Cells

“…C-C Motif Chemokine Ligand 2 (CCL2) is a member of the CC subfamily which is characterized by two adjacent cysteine residues [29]. The most described and best understood role of CCL2 so far is the recruitment of dendritic cells, monocytes and memory T cells to sites where inflammation has been triggered by injury or infection [30,31]. As in the genes described below, such a high expression of this gene could have been influenced by bacteria or their remains indispensable in primary cultures, as it has been proven that viral and bacterial infections result in high levels of, among others, CCL2 [32].…”