Phagocytosis

Jump to:  Single-Cell Approach || Target-Specific Phagocytosis || Phagocyte-Specific Phagocytosis || Recent Publications

SINGLE-CELL APPROACH

White blood cells form the frontline defense of our immune system against pathogenic invaders. Neutrophils, macrophages, and monocytes are capable of neutralizing foreign objects by phagocytosis.  This vital process depends on two complementary parts:  the timely recognition of pathogens, and the immune cells’ aptitude to change their shape and do mechanical work.  Much effort has been devoted to mapping the signaling networks involved in the detection, uptake, and processing of phagocytic targets. However, little is known about the fundamental mechanisms orchestrating the interplay between immune recognition and controlled cellular motion.We have pioneered an interdisciplinary approach to study the mechanistic underpinnings of one-on-one interactions between immune cells and various targets that mimic pathogens. It is based on dual-micropipette manipulation of individual cells and targets.  Typical experiments are illustrated in the movies below (sped up ~25 times):   Single-neutrophil/single-target phagocytosis of antibody-coated beads of different sizes: Experiments (top row) and simulations (bottom row) [Herant et al. 2006] [Click thumbnails to play movies in separate windows.]

	Advantages of this approach [Lee et al. 2011]:
	→ Experiments are based on a single-cell/single-target assay using live cells. → Phagocytes are non-adherent and quiescent prior to contact with a target. → Contacts between cells and targets are well controlled. → An essentially axisymmetric configuration makes the experiments uniquely amenable to quantitative analysis. → The experiments provide the time courses of several key parameters of phagocytosis for each cell, such as the position and speed of the target, or the cortical tension [Herant et al. 2005] of the phagocyte. → Drug-inhibition experiments are not limited to binary outcomes, but instead reveal which stages of phagocytosis are affected more or less by each inhibitor. → The experimental results can directly be compared to computer simulations [Herant et al. 2006 & 2011], which enables us to corroborate or discard hypotheses about the mechanoregulation of phagocytosis.

TARGET-SPECIFIC PHAGOCYTOSIS MECHANICS

The above single-cell approach has allowed us to discover, quantify, and explain intriguing differences between two prominent immunological pathways:  the response to fungal targets (mimicked using zymosan particles), and antibody-mediated phagocytosis [Lee et al. 2011; Herant et al. 2011].

 

	Movies below are sped up ~25-30 times.
	Neutrophil phagocytosis of a zymosan particle (left) and an antibody-coated bead (right). Top row: experiments. [Lee et al. 2011] Bottom row: computer simulations. [Herant et al. 2011] [Click thumbnails to play in separate windows.]

PHAGOCYTE-SPECIFIC MECHANICS OF PHAGOCYTOSIS

[Lam et al. 2009]

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RECENT PUBLICATIONS ON PHAGOCYTOSIS

2013. Mankovich, A.R., C.-Y. Lee, and V. Heinrich. Differential effects of serum heat treatment on chemotaxis and phagocytosis by human neutrophils. PLoS ONE 8(1): e54735. doi:10.1371/journal.pone.0054735 || PDF 907 KB

2011. Heinrich, V., and C.-Y. Lee. Blurred line between chemotactic chase and phagocytic consumption: An immunophysical, single-cell perspective. Journal of Cell Science 124(18):3041-3051. doi:10.1242/jcs.086413 || low-res. PDF 702 KB

2011. Lee, C.-Y., M. Herant, and V. Heinrich. Target-specific mechanics of phagocytosis: Protrusive neutrophil response to zymosan differs from the uptake of antibody-tagged pathogens. Journal of Cell Science 124(7):1106-1114. doi:10.1242/jcs.02876 || PDF 1104 KB

2011. Herant, M., C.-Y. Lee, M. Dembo, and V. Heinrich. Protrusive push versus enveloping embrace: Computational model of phagocytosis predicts key regulatory role of cytoskeletal membrane anchors. PLoS Computational Biology 7(1): e1001068. doi:10.1371/journal.pcbi.1001068 || PDF 274 KB

2009. Lam, J., M. Herant, M. Dembo, and V. Heinrich. Baseline mechanical characterization of J774 macrophages. Biophysical Journal 96:248-254. doi:10.1529/biophysj.108.139154 || PDF 768 KB

2006. Herant, M., V. Heinrich, and M. Dembo. Mechanics of neutrophil phagocytosis: experiments and quantitative models. Journal of Cell Science 119:1903-1913. doi:10.1242/jcs.02876 || PDF 727 KB

2005. Herant, M., V. Heinrich, and M. Dembo. Mechanics of neutrophil phagocytosis: behavior of the cortical tension. Journal of Cell Science 118(9):1789-1797. doi:10.1242/jcs.02275 || PDF 731 KB