A third measure-metastable state in the dynamics of spontaneous shape change in healthy human's white cells.

Karen A Selz

doi:10.1371/journal.pcbi.1001117

Abstract

Human polymorphonuclear leucocytes, PMN, are highly motile cells with average 12-15 µm diameters and prominent, loboid nuclei. They are produced in the bone marrow, are essential for host defense, and are the most populous of white blood cell types. PMN also participate in acute and chronic inflammatory processes, in the regulation of the immune response, in angiogenesis, and interact with tumors. To accommodate these varied functions, their behavior is adaptive, but still definable in terms of a set of behavioral states. PMN morphodynamics have generally involved a non-equilibrium stationary, spheroid Idling state that transitions to an activated, ellipsoid translocating state in response to chemical signals. These two behavioral shape-states, spheroid and ellipsoid, are generally recognized as making up the vocabulary of a healthy PMN. A third, “random” state has occasionally been reported as associated with disease states. I have observed this third, Treadmilling state, in PMN from healthy subjects, the cells demonstrating metastable dynamical behaviors known to anticipate phase transitions in mathematical, physical, and biological systems. For this study, human PMN were microscopically imaged and analyzed as single living cells. I used a microscope with a novel high aperture, cardioid annular condenser with better than 100 nanometer resolution of simultaneous, mixed dark field and intrinsic fluorescent images to record shape changes in 189 living PMNs. Relative radial roundness, R(t), served as a computable order parameter. Comparison of R(t) series of 10 cells in the Idling and 10 in the Treadmilling state reveals the robustness of the “random” appearing Treadmilling state, and the emergence of behaviors observed in the neighborhood of global state transitions, including increased correlation length and variance (divergence), sudden jumps, mixed phases, bimodality, power spectral scaling and temporal slowing. Wavelet transformation of an R(t) series of an Idling to Treadmilling state change, demonstrated behaviors concomitant with the observed transition.

Highlights

Polymorphonuclear neutrophil granulocytes (PMNs) are the body’s most abundant class of white blood cells
Once activated, idling PMNs exploit shape change dynamics as they tether to the endothelium of post-capillary venules, making and breaking bonds while rolling along the venule’s endothelial bed of selectins
PMN are generally observed in a spheroid Idling state transitioning to an activated, eggshaped, translocating state when triggered by the body’s signals of infection or inflammation

Summary

Introduction

Polymorphonuclear neutrophil granulocytes (PMNs) are the body’s most abundant class of white blood cells. Non-activated neutrophil circulates in the blood for 8 to 12 hours before undergoing apoptosis. Once activated, idling PMNs exploit shape change dynamics as they tether to the endothelium of post-capillary venules, making and breaking bonds while rolling along the venule’s endothelial bed of selectins. Following concentration gradients of inflammatory ligands, they wriggle through the vessel wall and migrate to the site of the initiating inflammation. The motions accompanying this migration exploit the PMN’s cytoskeletal, actin polymerization-depolymerization cycle that configures the dynamics of shape change and translation [5,6]

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Discussion

Conclusion