Characterization of biomechanical properties of cells through dielectrophoresis-based cell stretching and actin cytoskeleton modeling

Abstract

Background: Cytoskeleton is a highly dynamic network that helps to maintain the rigidity of a cell, and the mechanical properties of a cell are closely related to many cellular functions. This paper presents a new method to probe and characterize cell mechanical properties through dielectrophoresis (DEP)-based cell stretching manipulation and actin cytoskeleton modeling.

Methods: Leukemia NB4 cells were used as cell line, and changes in their biological properties were examined after chemotherapy treatment with doxorubicin (DOX). DEP-integrated microfluidic chip was utilized as a low-cost and efficient tool to study the deformability of cells. DEP forces used in cell stretching were first evaluated through computer simulation, and the results were compared with modeling equations and with the results of optical stretching (OT) experiments. Structural parameters were then extracted by fitting the experimental data into the actin cytoskeleton model, and the underlying mechanical properties of the cells were subsequently characterized.

Results: The DEP forces generated under different voltage inputs were calculated and the results from different approaches demonstrate good approximations to the force estimation. Both DEP and OT stretching experiments confirmed that DOX-treated NB4 cells were stiffer than the untreated cells. The structural parameters extracted from the model and the confocal images indicated significant change in actin network after DOX treatment.

Conclusion: The proposed DEP method combined with actin cytoskeleton modeling is a simple engineering tool to characterize the mechanical properties of cells.

Keywords: Cell stretching; Cytoskeleton model; Dielectrophoresis; Mechanical property; Optical tweezers.

Fig. 1

Experimental platform for dielectrophoresis-based cell stretching

Fig. 2

Microfluidic chip design. a Image of the chip; b schematic diagram showing the microelectrodes and the microchannel in the microfluidic chip; and c image captured under the microscope

Fig. 3

Deformation of an NB4 cell under different voltages: a the cell was captured at the electrode edge using 2 V_pp and then deformed under b 5 V_pp, c 8 V_pp; d the cell lysed under 9 V_pp. Deformation of an NB4-DOX cell: e the cell was captured at the electrode edge using 2 V_pp and then deformed under f 5 V_pp, g 8 V_pp, and h 9 V_pp

Fig. 4

COMSOL simulation showing the electric field distribution a without and b with the cell

Fig. 5

Strain–force curves of NB4 and NB4-DOX cells under DEP stretching (mean ± SE, NB4 cells: n = 54, NB4-DOX cells: n = 55)

Fig. 6

Strain–force curves of NB4 and NB4-DOX cells under optical tweezer (OT)-based stretching (mean ± SE, NB4 cells: n = 20, NB4-DOX cells: n = 20)

Fig. 7

Confocal images of actin cytoskeleton. a NB4 cells and b NB4-DOX cells (the scale bar is 10 μm)