title: A Film Tension Theory of Phagocytosis
abstract: A film tension criterion is derived on the basis of which it is possible to evaluate the probability of a particle or vesicle being phagocytosed by phagocytic cells. Variations of this criterion are arrived at by mechanical and thermodynamical analyses. Specific receptor-ligand binding interactions are included in the analysis, as are electrostatic, steric repulsive, and van der Waals attractive interactions between the surface of the phagocytosed particle and the pseudopods of the host cell membrane. Cytoskeletal forces proximate to the membrane are also implicitly included in the approach. The film tension criterion is shown to reduce to the classical wettability criterion in the limit of purely passive phagocytosis, wherein there are no electrostatic, steric repulsive, or receptor-ligand binding interactions between the cell and the phagocytosed particle. Several formulas characterizing various aspects of phagocytosis are derived. Opsonized particles are demonstrated to be more readily phagocytosed than nonopsonized particles, owing both to the energy of specific binding between opsonins and cell receptors and to the lowering of membrane tension that occurs in the vicinity of spreading pseudopods as a result of spontaneous actin polymerization. It is shown that certain particles or vesicles (those that are most easily phagocytosed) tend to be ingested more readily with increasing particle size, while others (those less easily phagocytosed) tend to be ingested more readily with decreasing size. In the limit of purely passive phagocytosis, formulas are developed for predicting the relative volumetric and particle-number uptake by cells as a function of organic/water partition coefficients. Partition coefficients of polystyrene particles and polymerized liposomes were measured and used to make theoretical predictions of particle uptake by macrophages. These predictions are compared with phagocytic uptake data for hydrophilic and hydrophobic nano- and microparticles. The comparisons show agreement between predicted trends of volumetric and particle-number uptake as a function of particle size, with uptake of hydrophilic nanoparticles diminishing with increasing size and uptake of hydrophobic nanoparticles increasing with increasing size (at least for submicrometer particles that are relatively insensitive to gravitational forces). Additional comparisons between published experimental data and theoretical predictions are also made. The potential use of the theory in characterizing the tendency of drug-loaded polymeric particles to be engulfed by macrophages is emphasized.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139
authors.initials: H
authors.lastname: Chen
authors.initials: R
authors.lastname: Langer
authors.initials: DA
authors.lastname: Edwards