In situ Microrheological Determination of Neutrophil Stiffening Following Adhesion in a Model Capillary

Abstract

There has been considerable debate on the relative importance of biochemical stimuli and mechanical deformation in neutrophil adhesion in lung capillaries, a process observed following bacterial infection in the body. In contrast to venules, where the vessel diameter is larger than the leukocyte diameter (6-9 microm) and the adhesion process is better understood, in lung capillaries the vessel diameter (2-8 microm) is smaller than the leukocyte diameter. In this study, a micropipette was used as a model for the alveolar capillary microcirculation, allowing the effects of adhesion molecules (ICAM-1) on cell mechanical properties to be observed while applying a mechanical deformation. The microrheology technique that tracks the thermal motion of granules within neutrophils was used to extract the local intracellular viscoelastic moduli. Small regional differences in rheology were found, with the central body region being significantly stiffer than the leading end cap region. When cells were exposed to ICAM-1, the regional differences were preserved, but the viscoelastic moduli were moderately increased in all regions. These results are consistent with the literature on leukocyte sequestration and provide insight into the regional rheological effects of deformation and adhesion molecules on neutrophils.