Investigating the role of calcium in the biomechanical response of neutrophils to mechanical deformation experienced in the pulmonary capillaries
Author(s)Hsu, Jeffrey J
Massachusetts Institute of Technology. Biological Engineering Division.
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Neutrophils in the pulmonary microcirculation are subjected to mechanical deformation while traveling through capillaries of sizes much smaller than the mean neutrophil diameter. This deformation has been shown to result in significant reductions in both the shear storage and shear loss moduli of the cell, with subsequent recovery towards their initial values. Also, deformation above a threshold stimulus results in neutrophil activation, evidenced by pseudopod projection from the cell. These two events are thought to occur via independent pathways, yet little is known about the mechanosensing signaling involved. Other work has demonstrated that physiological deformation of neutrophils induces a marked increase in the levels of cytosolic calcium, suggesting that this occurrence may trigger the biomechanical response observed in the cell. The aim of this thesis was to elucidate the role of calcium in the neutrophil response to the mechanical deformation experienced during transit through the pulmonary capillaries.(cont.) Chelating intracellular calcium in neutrophils resulted in (i) decreased deformability of the cells into a microchannel, (ii) attenuation of the drop in shear storage modulus (G') observed in untreated cells upon deformation, and (iii) shorter activation times. These findings suggest that cytosolic calcium holds an important function in the neutrophil transit through the capillaries, and inhibition of normal calcium release within the cell can lead to leukostasis-like conditions.
Thesis (M. Eng.)--Massachusetts Institute of Technology, Biological Engineering Division, 2006.Includes bibliographical references (p. 73-79).
DepartmentMassachusetts Institute of Technology. Biological Engineering Division.
Massachusetts Institute of Technology
Biological Engineering Division.