Abstract. Processes such as cell locomotion and morphogenesis depend on both the generation of force by cytoskeletal elements and the response of the cell to the resulting mechanical loads. Many widely accepted theoretical models of processes involving cell shape change are based on untested hypotheses about the interaction of these two components of cell shape change . I have quantified the mechanical responses of cytoplasm to various chemical environments and mechanical loading regimes to understand better the mechanisms of cell shape change and to address the validity of these models. Measurements of cell mechanical properties were made with strands of cytoplasm submerged in media containing detergent to permeabilize the plasma FUNDAMENTALtounderstandingboth morphogenesis and cell locomotion is an understanding of the mechanisms of cell shape changes. Current ideas about those mechanisms are based largely on two types of approaches : (a) mathematical modeling (e.g., Odell et al ., 1981;Mittenthal and Mazo, 1983;Oster et al., 1983 ;White and Borisy, 1983;Oster and Odell, 1984;Belintsev et al., 1987); and (b) experimental characterization ofthe distribution and activity of microfilament-and microtubule-based force generating systems (e.g., Byers and Porter, 1964;Pollard and Ito, 1970;Spooner and Wessells, 1972;Burnside, 1973 ;Stopak and Harris, 1982;Priess and Hirsh, 1986) . Less frequently examined, although equally critical, are the responses of the cell to the mechanical loads imposed on them by their cytoskeletons or by external forces (Waddington, 1942;Odell et al., 1981;Condeelis, 1983 ;Elson, 1988) . Those responses are prescribed by mechanical properties of the cell such as stiffness, elasticity, and viscosity.Although many researchers have contributed to the task of characterizing the mechanical properties of cytoplasm (e.g ., Seifriz, 1952;Hiramoto, 1970Hiramoto, , 1976Yoshimoto and Kamiya, 1978;Achenbach and Wohlfarth-Bottermann, 1980;Matsumura et al., 1980;Sato et al ., 1983) no one has yet produced a comprehensive description that considers both the nature of the loads and their time history (Elson, 1988) . As a result, mathematical models of morphogenesis have re-© The Rockefeller University Press, 0021-9525/92/04/83/11 $2 .00 The Journal of Cell Biology, Volume 117, Number 1, April 1992 83-93 membrane, thus allowing control over intracellular milieu . Experiments were performed with equipment that generated sinusoidally varying length changes of isolated strands of cytoplasm from Physarum polycephalum. Results indicate that stiffness, elasticity, and viscosity of cytoplasm all increase with increasing concentration of Cal+, Mgt+, and ATP, and decrease with increasing magnitude and rate of deformation . These results specifically challenge assumptions underlying mathematical models of morphogenetic events such as epithelial folding and cell division, and further suggest that gelation may depend on both actin crosslinking and actin polymerization.lied largely on postulated mechanical properties rat...