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. 2021 Dec 2;25(1):103555.
doi: 10.1016/j.isci.2021.103555. eCollection 2022 Jan 21.

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

Tom M J Evers  1 , Vahid Sheikhhassani  1 , Mariëlle C Haks  2 , Cornelis Storm  3 , Tom H M Ottenhoff  2 , Alireza Mashaghi  1
Affiliations

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

Tom M J Evers et al. iScience. .

Abstract

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.

Keywords: Biomechanics; Cell biology; Immunology.

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Conflict of interest statement

The authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Human monocyte mechanics is affected by strain rate and CCL2 treatment (A) Schematic representation of OT, in which a monocyte is sandwiched between two optically trapped beads. (B) Morphological changes of a monocyte after treatment with 200 ng/mL of CCL2 for 15 min prior to bead attachment. (C) Typical trace of recorded force versus time at RT, PT, and upon stimulation by CCL2. (D) Dynamic stiffness of monocytes at RT, PT, and after treatment with CCL2 fitted by a power law model. CCL2-treated cells could not be fitted by the power-law function, and only data points are shown. (E) Power exponent of stress-relaxation analysis as a function of strain rate at RT and PT showed a significant difference (p < 0.0001). (F) In case of CCL2-treated cells, power exponent revealed strain-rate dependent changes; 0.20 ± 0.04 for velocities from 1 to 5 μm/s and 0.36 ± 0.03 for velocities from 7 to 20 μm/s (p value = 0.002). Data are represented as mean ± SEM.
Figure 2
Figure 2
CCl2 alters the viscoelastic properties of human monocytes, measured with AFS (A) Magnified image of the flow chamber showing a typical field of view in experiments. Tens of beads on top of the monocytes are individually tracked. (B) Further magnified image of the typical field of view showing single monocytes with beads attached on top. (C) Typical trace (creep compliance) of a monocyte in response to the application of a constant force (3.5 nN) at physiological temperature and after exposure to CCL2. (D) Schematic representations of the KV and SLL model. (E) CCL2 induces a significant increase in the average elastic modulus Em of monocytes (p < 0.0001). (F) CCL2 induces a significant increase in the viscosity η of monocytes (p < 0.0001). (G) CCL2 significantly increases the average elastic modules Ea associated with the cytoskeleton (p < 0.0001). (H) CCL2 significantly increases the average viscosity ηa associated with the cytoskeleton (p <0.0001). (I) The average background viscosity ηc of monocytes significantly increases upon stimulation by CCL2 (p <0.0001). Distributions plotted using Origin-Lab (2019b). p-values calculated using Mann-Whitney test.
Figure 3
Figure 3
Graphical summary of the effects of strain rate and CCL2 treatment on monocyte mechanics, measured with OT and AFS. The figure illustrates how two fundamentally distinct modes of regulation, namely regulations through chemical and mechanical stimulations modulate monocyte mechanics. Mechanical strain increases the stiffness and elastic modulus, and decreases the viscosity of monocytes. Chemical stimulation by CCL2 induces an increase in both elastic modulus and viscosity. Simultaneous mechanical and chemical stimulation of monocytes lead to increased elastic modulus at lower stretching velocities, and increased viscosity and stiffness at higher velocities.
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