Abstract
AimsMonocytes play a significant role in the development of atherosclerosis. During the process of inflammation, circulating monocytes become activated in the blood stream. The consequent interactions of the activated monocytes with the blood flow and endothelial cells result in reorganization of cytoskeletal proteins, in particular of the microfilament structure, and concomitant changes in cell shape and mechanical behavior. Here we investigate the full elastic behavior of activated monocytes in relation to their cytoskeletal structure to obtain a better understanding of cell behavior during the progression of inflammatory diseases such as atherosclerosis.Methods and ResultsThe recently developed Capillary Micromechanics technique, based on exposing a cell to a pressure difference in a tapered glass microcapillary, was used to measure the deformation of activated and non-activated monocytic cells. Monitoring the elastic response of individual cells up to large deformations allowed us to obtain both the compressive and the shear modulus of a cell from a single experiment. Activation by inflammatory chemokines affected the cytoskeletal organization and increased the elastic compressive modulus of monocytes with 73–340%, while their resistance to shape deformation decreased, as indicated by a 25–88% drop in the cell’s shear modulus. This decrease in deformability is particularly pronounced at high strains, such as those that occur during diapedesis through the vascular wall.ConclusionOverall, monocytic cells become less compressible but more deformable upon activation. This change in mechanical response under different modes of deformation could be important in understanding the interplay between the mechanics and function of these cells. In addition, our data are of direct relevance for computational modeling and analysis of the distinct monocytic behavior in the circulation and the extravascular space. Lastly, an understanding of the changes of monocyte mechanical properties will be important in the development of diagnostic tools and therapies concentrating on circulating cells.
Highlights
Atherosclerosis is a chronic inflammatory disease that affects mainly large and medium sized arteries
Overall, monocytic cells become less compressible but more deformable upon activation. This change in mechanical response under different modes of deformation could be important in understanding the interplay between the mechanics and function of these cells
An understanding of the changes of monocyte mechanical properties will be important in the development of diagnostic tools and therapies concentrating on circulating cells
Summary
Atherosclerosis is a chronic inflammatory disease that affects mainly large and medium sized arteries. Circulating monocytes, which form a small subpopulation of the leukocytes, are well known to be involved in the disease progression [1,2]. Investigating the evolution of monocyte mechanical behavior might lead to a better understanding of the progression of the disease and the development of viscoelastic mechanical models clarifying the abnormal behavior of monocytes in circulation. During the process of inflammation, monocytes become activated in the blood stream. Upon activation, they adhere to the endothelium and, in a process called diapedesis, extravasate through the endothelium to migrate to the target tissue. The cytoskeleton has the ability to rapidly regulate the amount and the architecture of its protein components in response to inflammatory cytokines to enable cells to fulfill their function [3]
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