Physical Constraints and Forces Involved in Phagocytosis

Abstract

Phagocytosis is a specialized process that enables cellular ingestion and clearance of microbes, dead cells and tissue debris that are too large for other endocytic routes. As such, it is an essential component of tissue homeostasis and the innate immune response, and also provides a link to the adaptive immune response. However, ingestion of large particulate materials represents a monumental task for phagocytic cells. It requires profound reorganization of the cell morphology around the target in a controlled manner, which is limited by biophysical constraints. Experimental and theoretical studies have identified critical aspects associated with the interconnected biophysical properties of the receptors, the membrane, and the actin cytoskeleton that can determine the success of large particle internalization. In this review, we will discuss the major physical constraints involved in the formation of a phagosome. Focusing on two of the most-studied types of phagocytic receptors, the Fcγ receptors and the complement receptor 3 (αMβ2 integrin), we will describe the complex molecular mechanisms employed by phagocytes to overcome these physical constraints.

FisB relies on homo-oligomerization and lipid-binding to catalyze membrane fission in bacteria

“…Membrane fission is a fundamental process required for endocytosis 1 , membrane trafficking 2 , enveloped virus budding 3 , phagocytosis 4 , cell division 5 and sporulation [6][7][8] . During membrane fission, an initially continuous membrane divides into two separate ones.…”

Micro-topographical guidance of macropinocytic signaling patches

“…In immune-cells, phagocytosis involves a zippering mechanism where the advancing rim of a cup protrudes sequentially by forming an anchorage with the specific surface signal, and the membrane maintains close contact with the surface to gain traction (Jaumouillé and Waterman, 2020; Swanson and Baer, 1995). Macropinocytic cup formation, on the other hand, does not require such specific anchorage and traction (Jaumouillé and Waterman, 2020; Swanson and Baer, 1995). To see whether non-zipper type cup formation is able to capture a ridge, we tested a minimal model of macropinocytic cup formation (Saito and Sawai, 2020).…”

“…Phagocytosis often refers to specific adhesion-dependent engulfment in immune cells, where the surface of the ingesting particle is decorated with opsonins; i.e. scaffold antigens or complements which through membrane-bound receptor signaling (Swanson, 2008) processively extends the protruding edge of the cup along the attached solid surface (Case and Waterman, 2015; Jaumouillé and Waterman, 2020). Macropinocytosis on the other hand refers to a self-organizing process where the shaping of the membrane by the branched actin meshworks does not require a solid surface (Swanson, 2008) and can occur constitutively (Williams and Kay, 2018).…”

More than just a barrier: using physical models to couple membrane shape to cell function

“…For mammals the ability to phagocytose particles is mainly limited to immune cells to clear out pathogens, whereas single-cell organisms use it to take up nutrients. [137][138][139] Although the actual dynamics have not been fully resolved experimentally, phagocytosis can be modeled by a zipper mechanism, implying that phagocytosis is the collective interplay of many particle-membrane adhesion contacts. In detail, first particles adhere to the plasma membrane through sequential ligand-receptor binding.…”

“…Finally, the membrane fuses around the particle to enable the separation of the enveloped particle from the plasma membrane. 137,139 In contrast to adhesion driven particle uptake, the particle size does not seem to play an important role for the effectiveness of phagocytosis, 140 suggesting that active processes are the dominant players involved. Indeed large particles are engulfed not just by the membrane but also by the growing actin cortex.…”