Cell Motility and Local Viscoelasticity of Fibroblasts

Abstract

Viscoelastic changes of the lamellipodial actin cytoskeleton are a fundamental element of cell motility. Thus, the correlation between the local viscoelastic properties of the lamellipodium (including the transitional region to the cell body) and the speed of lamellipodial extension is studied for normal and malignantly transformed fibroblasts. Using our atomic force microscopy-based microrheology technique, we found different mechanical properties between the lamellipodia of malignantly transformed fibroblasts (H-ras transformed and SV-T2 fibroblasts) and normal fibroblasts (BALB 3T3 fibroblasts). The average elastic constants, K, in the leading edge of SV-T2 fibroblasts (0.48 +/- 0.51 kPa) and of H-ras transformed fibroblasts (0.42 +/- 0.35 kPa) are significantly lower than that of BALB 3T3 fibroblasts (1.01 +/- 0.40 kPa). The analysis of time-lapse phase contrast images shows that the decrease in the elastic constant, K, for malignantly transformed fibroblasts is correlated with the enhanced motility of the lamellipodium. The measured mean speeds are 6.1 +/- 4.5 microm/h for BALB 3T3 fibroblasts, 13.1 +/- 5.2 microm/h for SV-T2 fibroblasts, and 26.2 +/- 11.5 microm/h for H-ras fibroblasts. Furthermore, the elastic constant, K, increases toward the cell body in many instances which coincide with an increase in actin filament density toward the cell body. The correlation between the enhanced motility and the decrease in viscoelastic moduli supports the Elastic Brownian Ratchet model for driving lamellipodia extension.

SLK-mediated phosphorylation of paxillin is required for focal adhesion turnover and cell migration

“…Actin fibres, by mass, are the dominant structural element of actively moving cellular extensions, and are the most abundant protein in a eukaryotic cell [11,12]. Specifically, lamellipodial extension is regulated by the dynamic polymerization of actin in a Rac1 and Cdc42-dependent manner into branched filament networks.…”

Get round and stiff for mitosis

“…They are rigid and contractile (Rotsch et al, 1999;Rotsch and Radmacher, 2000;Peterson et al, 2004). On adhesive regions, actin filaments assemble in a meshwork which is much softer (Laurent et al, 2005;Park et al, 2005). The growth of this meshwork pushes on the cell periphery and induces membrane protrusions.…”

Nano-biomechanical Validation of Epithelial–Mesenchymal Transition in Oral Squamous Cell Carcinomas

“…18) Until recently, a substantial level reorganization of actin filaments was noticed as a major cause responsible for mechanical changes in cancer cells. 25,36,37) However, only a few studies investigated the possible significance of other components such as keratins in cancer progression. 38,39) Vimentin, one of the intermediate filaments, is known to be overexpressed in various epithelial cancers.…”

“…23) The decrease in the mechanical stiffness revealed by AFMbased biomechanics was suggested to be a promising marker for cancer diagnosis. 18,24,25) However, the relationship between the mechanical stiffness and the metastatic potential of cancer cells has not been unequivocally established. Some studies reported the decrease in the mechanical stiffness as a mechano-phenotypic feature of metastatic cancer cells.…”