Mechanisms of cell shape change: the cytomechanics of cellular response to chemical environment and mechanical loading

Abstract

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...

Dynamic study of cell mechanical and structural responses to rapid changes of calcium level

“…Our conclusion that calcium rise induced a transient stiffening followed by a delayed deformability increase is consistent with the previous report that the disruption of stress fibers by endogenous gelsolin might require a durable increase of cytoplasmic calcium [Kanno and Sasaki, 1989]. This may also account for some discrepancy in reported data: indeed, increasing intracellular calcium increased the rigidity of rat basophilic leukemia cells [Horoyan et al, 1990] or isolated cytoplasmic strands [Adams, 1992], but Fig. 10.…”

“…Leukocyte transmigration from blood towards inflamed peripheral tissues involves impressive squeezing between endothelial cells [Marchesi, 1961]. Also, processes such as locomotion or spreading are dependent on both force generation and cell response to the resulting mechanical loads [Adams, 1992]. Further, a cell may need to regulate its deformability.…”

Fluid shear stress differentially modulates expression of genes encoding basic fibroblast growth factor and platelet-derived growth factor B chain in vascular endothelium.

“…7 and five separate experiments revealed no significant difference in bFGF mRNA level between steady laminar and turbulent, and be- This result suggests that the magnitude of the shear stress stimulus is a more important determinant of bFGF and PDGF-B mRNA levels than the dynamic characteristics ofthe t= 36 dynes/cm2 shear stress at a given time-average magnitude, at least for the N=240 four conditions employed in this study. These findings suggest o=1 0.70 that the endothelial cell, which may be modeled as a viscoelastic structure (40,41 ), behaves as a sensor to the low frequency (average magnitude) of the shear stress stimulus rather than to its higher frequency components (turbulent or pulsatile There has been mounting evidence to suggest that blood flow, and more specifically the resulting shear stress acting on the vessel wall at the endothelial cell, plays a central role in determining vascular structure ( 1, 5, 6) by a process that is dependent on intact endothelium (6). Recent work has also demonstrated that fluid shear stress changes physiological properties of endothelial cells ( 10-1 2, 15, 42).…”

Four-dimensional imaging of living chondrocytes in cartilage using confocal microscopy: a pragmatic approach

“…Thus chondrocytes are exposed to a dynamic ionic and osmotic environment. Potentially, chondro cytes exploit changes in extracellular mechanical and chemical information to modulate their physiological and metabolic behavior (1). Indeed, it has been shown that the osmotic and ionic environment influences matrix metabolism (28, 34); therefore, it is important to understand chondrocyte volume regulation in the face of such environmental challenges.…”