Modeling cytoadhesion of Plasmodium falciparum‐infected erythrocytes and leukocytes—common principles and distinctive features

Abstract

Cytoadhesion of Plasmodium falciparum‐infected erythrocytes to the microvascular endothelial lining shares striking similarities to cytoadhesion of leukocytes. In both cases, adhesins are presented in structures that raise them above the cell surface. Another similarity is the enhancement of adhesion under physical force (catch bonding). Here, we review recent advances in our understanding of the molecular and biophysical mechanisms underlying cytoadherence in both cellular systems. We describe how imaging, flow chamber experiments, single‐molecule measurements, and computational modeling have been used to decipher the relevant processes. We conclude that although the parasite seems to induce processes that resemble the cytoadherence of leukocytes, the mechanics of erythrocytes is such that the resulting behavior in shear flow is fundamentally different.

Rolling Adhesion of Schizont Stage Malaria-Infected Red Blood Cells in Shear Flow

“…5 A, the on-off state diagram is shown for N R ¼ 1000 unclustered receptors at shear rate _ g ¼ 100 Hz. We find very good agreement with earlier results (36,44,46), and in the following we use this state diagram as a reference case. Free motion and transient adhesion-1 are achieved at high off-rates and low on-rates, where the number of bonds become almost negligible, allowing the cell to move freely in shear flow.…”

“…Regarding computer simulations, the model is adapted from rolling adhesion of WBCs (44), as schizont stage iRBCs share many common features with leukocytes (36). The model cell is assumed to have a spherical shape covered with adhesive knobs containing the PfEMP-1 receptors that mediate adhesion to ligands such as ICAM-1 presented by the vascular endothelium.…”

“…To classify different dynamic states, we adopt a classification scheme based on the averages and variances of the translational and angular velocities (36,44). Each cell trajectory belongs to one of the five dynamic states, namely free motion, transient motion-1, transient motion-2, rolling adhesion, and firm adhesion.…”

“…In contrast to the iRBCs, WBCs use receptors from the selectin-family for capture and rolling, and these are localized to hundreds of microvilli rather than thousands of knobs. Yet the basic design principle (elevated platforms for adhesion receptors distributed over a roundish cell shape) is very similar and therefore iRBC-rolling can be considered as mimicry of WBC-rolling (36). In particular, flow chamber experiments are also commonly used to study rolling adhesion of iRBCs (19,23,27,37).…”

A 1D model of leukocyte adhesion coupling bond dynamics with blood velocity

“…The nature of the bonds (slip and/or catch) has been the source of active debate during the last decades (Bell (1978) for slip bond description, Finger et al (1996) for catch bond and see Korn (2007); Ley et al (2007); Helms et al (2016) and references therein for more details).…”