Email updates

Keep up to date with the latest news and content from BMC Systems Biology and BioMed Central.

Open Access Highly Accessed Research article

The zipper mechanism in phagocytosis: energetic requirements and variability in phagocytic cup shape

Sylvain Tollis12, Anna E Dart23, George Tzircotis23 and Robert G Endres12*

Author Affiliations

1 Division of Molecular Biosciences, South Kensington Campus, Imperial College London, SW72AZ London, UK

2 Centre for Integrative Systems Biology at Imperial College (CISBIC), South Kensington Campus, Imperial College London, SW72AZ London, UK

3 Division of Cell and Molecular Biology, South Kensington Campus, Imperial College London, SW72AZ London, UK

For all author emails, please log on.

BMC Systems Biology 2010, 4:149  doi:10.1186/1752-0509-4-149

Published: 8 November 2010

Abstract

Background

Phagocytosis is the fundamental cellular process by which eukaryotic cells bind and engulf particles by their cell membrane. Particle engulfment involves particle recognition by cell-surface receptors, signaling and remodeling of the actin cytoskeleton to guide the membrane around the particle in a zipper-like fashion. Despite the signaling complexity, phagocytosis also depends strongly on biophysical parameters, such as particle shape, and the need for actin-driven force generation remains poorly understood.

Results

Here, we propose a novel, three-dimensional and stochastic biophysical model of phagocytosis, and study the engulfment of particles of various sizes and shapes, including spiral and rod-shaped particles reminiscent of bacteria. Highly curved shapes are not taken up, in line with recent experimental results. Furthermore, we surprisingly find that even without actin-driven force generation, engulfment proceeds in a large regime of parameter values, albeit more slowly and with highly variable phagocytic cups. We experimentally confirm these predictions using fibroblasts, transfected with immunoreceptor Fc╬│RIIa for engulfment of immunoglobulin G-opsonized particles. Specifically, we compare the wild-type receptor with a mutant receptor, unable to signal to the actin cytoskeleton. Based on the reconstruction of phagocytic cups from imaging data, we indeed show that cells are able to engulf small particles even without support from biological actin-driven processes.

Conclusions

This suggests that biochemical pathways render the evolutionary ancient process of phagocytic highly robust, allowing cells to engulf even very large particles. The particle-shape dependence of phagocytosis makes a systematic investigation of host-pathogen interactions and an efficient design of a vehicle for drug delivery possible.