How cells engulf: a review of theoretical approaches to phagocytosis

Abstract

Phagocytosis is a fascinating process whereby a cell surrounds and engulfs particles such as bacteria and dead cells. This is crucial both for single-cell organisms (as a way of acquiring nutrients) and as part of the immune system (to destroy foreign invaders). This whole process is hugely complex and involves multiple coordinated events such as membrane remodelling, receptor motion, cytoskeleton reorganisation and intracellular signalling. Because of this, phagocytosis is an excellent system for theoretical study, benefiting from biophysical approaches combined with mathematical modelling. Here, we review these theoretical approaches and discuss the recent mathematical and computational models, including models based on receptors, models focusing on the forces involved, and models employing energetic considerations. Along the way, we highlight a beautiful connection to the physics of phase transitions, consider the role of stochasticity, and examine links between phagocytosis and other types of endocytosis. We cover the recently discovered multistage nature of phagocytosis, showing that the size of the phagocytic cup grows in distinct stages, with an initial slow stage followed by a much quicker second stage starting around half engulfment. We also address the issue of target shape dependence, which is relevant to both pathogen infection and drug delivery, covering both one-dimensional and two-dimensional results. Throughout, we pay particular attention to recent experimental techniques that continue to inform the theoretical studies and provide a means to test model predictions. Finally, we discuss population models, connections to other biological processes, and how physics and modelling will continue to play a key role in future work in this area.

Heterogeneity in the endocytic capacity of individual macrophage in a population determines its subsequent phagocytosis, infectivity and subcellular trafficking

“…Analogous to phagocytosis, endocytosis involves uptake of a variety of different cargo that are much smaller in size, using mechanisms that are both cargo‐specific and general 7,8 . Although endocytosis and phagocytosis share significant molecular machinery and processes, and are considered as portals for entry into cell, 3,7 emerging consensus attest to significant distinctness of the two processes at multiple levels 3,9,10 …”

Measuring stepwise binding of a thermally fluctuating particle to a cell membrane without labeling

“…The endocytic uptake of particles into cells is controlled by multiple biochemical and biophysical mechanisms. The most prominent cellular process, phagocytosis [1][2][3], comprises the engulfment, internalization and intracellular transport of a particle, requiring energy for the deformation of the cell membrane, the reorganization of the actin network [4] and for phagosome transport by molecular motors [5,6]. In many cases endocytosis is receptor-mediated, which means that ligands on particles, typically bacteria and viruses, trigger the recruitment of receptors in the cell membrane, such as the Fc receptor for immunoglobulins (Ig) or receptors of the complement system.…”

Stretchable and Reactive Membranes of Metal–Organic Framework Nanosurfactants on Liquid Droplets Enable Dynamic Control of Self‐Propulsion, Cargo Pick‐Up, and Drop‐Off

“…[4,[9][10][11][12] Such functions may derive from surface tension effects setting up gradients and flows [13][14][15] to which the components of a system may respondaccordingly, various types of stimulus-responsive surfactants have been developed on scales from molecular [16][17][18][19] to nano, [20,21] and microscopic. [27,28,34] It is envisioned that if these proof-of-theconcept demonstrations are furthermore developed, they can find uses in active droplet-based chemical systems [28,35] and emulsions capable of various pick-up/drop-off tasks, possibly with applications in waste remediation.As surface-active species, cubic particles of Zeolitic Imidazolate Framework-67 (ZIF-67) with an edge length of L ¼ 430 AE 50 nm and synthesized in aqueous solution according to a literature One way to achieve a comparable wealth of dynamic behaviors is to mimic biological systems and interface the surfactant species with molecular motors, cytoskeletal fibers, or other supra-molecular "machines".…”

“…[29][30][31] Another approachwithout precedent in biology-can be to integrate multiple dynamic functions, both mechanical and chemical, into the surfactants themselves. [27,28,34] It is envisioned that if these proof-of-theconcept demonstrations are furthermore developed, they can find uses in active droplet-based chemical systems [28,35] and emulsions capable of various pick-up/drop-off tasks, possibly with applications in waste remediation. [21] Herein, we demonstrate another form of functional integration, this time using crystals (few hundred nm in size) of porous, metal-organic frameworks (MOF) [32,33] that form dynamic monolayer "membranes" at interfaces between water droplets and the surrounding organic phase.…”

“…bottom right panel of Figure S10, Supporting Information). It is believed similar principles could be useful in constructing the so-called artificial cells [27,34,52] capable of primitive "phagocytosis" controlled by external stimuli. Here, the droplet contains 1 mM Na 2 CO 3 gel soaked with 1 mM FeCl 3 .…”