Physical Model for Phagocyte Motility: Local Growth of a Contractile Network from a Passive Body

Abstract

The scavenger cells of the reticulo-endothelial system are essential elements in an animal’s defense against invasion by pathogens. Many of these cells (granulocytes and monocytes) must recognize and engulf particles while n a convected suspension (blood) or they must attach to a vascular surface and move through the lining from the blood stream into the adjacent tissues to carry out their function. These significant tasks demand strong adhesivity, exceptional deformability, and powerful motility. Large extensions are made possible by redundancy in the plasma membrane envelope that surrounds the cell cytoplasm (~ 110% area in excess of the sphericalcell form — Schmid-Schonbein et al, 1980; Evans and Yeung, 1989). Usually, such redundancy would lead to conformational instability and easy fragmentation of the membrane; however, a subsurface cytoskeletal structure is present to stabilize the shape. For phagocytes, the subsurface structure appears to be a cortical network (Southwick and Stossel, 1983; Stossel et al, 1980; Valerius et al, 1981; Hartwig and Yin, 1988) of actin filaments attached to the membrane in a way that is not well understood. Although this arrangement seems similar to a simple red cell membrane, there are major differences. Principal is network contractility which, even in the passive cell state, creates a small persistent tension (Evans, 1984; Evans and Yeung, 1989); cortical contraction causes the plasma membrane envelope to gather and ruffle into many wrinkles and folds. In the passive state, these cells appear as nearly perfect spherical shapes which deform like highly viscous liquid drops (but the effective viscosity is 105 × that of water — Valberg and Feldman, 1987; Evans and Yeung, 1989); the cortical tension is the dominant elastic restoring force (Evans, 1984; Evans and Yeung, 1989; Dong et al, 1988). On the other hand, when activated, the cell erupts to produce major projections of cytoplasm that create motion on a substrate- or engulf particles- by progressive traction. Evidence supports the view that polymerization and growth of a filamentous-actin network drives these cytoplasmic projections (Stossel, 1984; Hartwig et al, 1985). The biochemistry of actin polymerization has been extensively investigated to provide a complex picture of regulation and growth (Griffith and Pollard, 1982; Pollard and Cooper, 1986). Based on these in vitro studies, the actin concentration in cells appears to exceed the critical concentration required to initiate polymerization; thus, free monomer is predicted to exist in a blocked form called profilactin which is a complex of G actin and profilin. After the complex is dissociated, actin monomers are added to the filamentous F actin network primarily at one end (called the “barbed end”) which can also be blocked by other actin binding proteins (e.g. gelosin). The polymerization reactants appear to be concentrated in a cortical layer adjacent to the plasma membrane (Hartwig and Yin, 1988; Stossel, 1984) and are mediated by many factors (phosphoinositides, Ca++ etc).