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Cell Motility and Local Viscoelasticity of Fibroblasts

S. Park ^*, D. Koch , R. Cardenas ^*, J. Käs  and C. K. Shih ^*  

^* Department of Physics, Texas Materials Institute, and Center for Nano and Molecular Science, University of Texas, Austin, Texas 78712; and Fakultät für Physik und Geowissenschaften, Universität Leipzig, D-04103 Leipzig, Germany

Correspondence: Address reprint requests to Soyeun Park at her present address, Dept. of Biomedical Engineering, University of Texas, Austin, TX 78712. E-mail: sypark20{at}physics.utexas.edu.

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 µ m/h for BALB 3T3 fibroblasts, 13.1 ± 5.2 µm/h for SV-T2 fibroblasts, and 26.2 ± 11.5 µm/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.