Microfluidic Rheology to Study Effects of Cell Cycle to Viscoelastic Properties of Epithelial Cells

Abstract

We introduce a microfluidic rheology platform to measure the viscoelastic properties of cells in different cell cycle stages. While there are a growing number of studies on cell mechanical properties, only a few have investigated these properties during cell-cycle progression in which there are significant changes in the cytoskeleton. Currently, atomic force microscopy (AFM) is the preferred method for cell micro-rheology due to its high resolution and high precision in loading frequency. However, its low throughput could be a critical limitation to correlate biophysical properties of cells with specific cell-cycle stage due to small sample size. Here, we propose a high throughput platform that employs microfluidics and electrical sensing to quantify cellular viscoelastic properties at the single cell level. Our microfluidic rheometer consists of a PDMS mold bonded to a glass substrate with predefined platinum electrodes. The mold consists of a microfluidic channel that has two central features: a node-pore pair and a sinusoidal-shaped contraction channel. As a cell transits the node-pore pair, a current pulse is recorded whose magnitude reflects cell size. As it transits the contraction channel, a cell undergoes periodic deformation due to the periodically changing channel width. The magnitude and frequency of cellular deformation is reflected in the subsequent current pulse produced. Combining these measured parameters with the fluidic conditions under which they were obtained, we can quantify cell storage and loss moduli. With our platform, we show that epithelial cells (MCF7 and MCF10A) have distinct viscoelastic properties that reflect their malignant status. Even within one cell population, however, we find that there is a variation in storage modulus. In this study, we focus on the origin of this variation and the specific role cell-cycle progression plays in altering whole-cell viscoelastic properties.