SYNCHRONY OF CELL SPREADING AND CONTRACTION FORCE AS PHAGOCYTES ENGULF LARGE PATHOGENS

A simple micromechanical method has been used to directly measure the force of contraction in single mammalian phagocytes (blood granulocyte s) during engulfment of large yeast pathogens. Both the time course of cell spreading over the yeast particle and increase in cell body cont ractile force were quantitated at three temperatures in the range of 2 3-35-degrees-C. The surprising feature of the phagocyte response was t hat engulfment and cell body contraction occurred in a serial sequence : i.e., the phagocyte spread rapidly over the particle at a steady rat e with no detectable cell body contraction; when spreading stopped, co ntraction force in the cell body then rose steadily to a plateau level that remained stationary until the next sequence of spreading and con traction. Both spreading and contraction exhibited abrupt start/stop k inetics. Also impressive, the cell contraction force stimulated by pha gocytosis was quite large (approximately 10(-8) N)-two orders of magni tude larger than the force necessary to deform passive phagocytes to t he same extent. If distributed uniformly over the cell cross section, the contraction force is equivalent to an average contractile stress o f approximately 10(3) N/m2 (0.01 Atm). These physical measurements in situ set critical requirements for the mechanism of force generation i n granulocytes, imply that a major increase in network cross-linking a ccompanies build-up in contractile force and that subsequent network d issolution is necessary for locomotion.