Direct Characterization of Stress-Strain Relationship for Quantifying Single Cell Elasticity

Abstract

The mechanical properties of live cells are important for maintaining cell physiological functions. Many types of cells such as cancer cells, malaria-infected cells, and cells with progeria have shown altered mechanical properties. Measurement of cell mechanics becomes useful for understanding cell physiology and potentially for diagnosing diseases. A number of techniques have been applied to measuring single cell mechanical properties, among which Atomic Force Microscopy (AFM) is a popular method. However, since this approach has an intrinsic problem of lacking contact area information, the elastic property were commonly extracted by fitting the force-displacement curve acquired from AFM indentation using a Hertzian contact model, which leads to inaccurate measurement as cell-probe contact violates the assumptions of Hertzian model (rigid body contact, no adhesion). An ideal approach to quantify cell's elastic property is direct compression or tensile testing which does not rely on any contact mechanics models with assumptions that cells might not be eligible for. Here, we quantified the elastic property of live cells directly from stress-strain curves by compression test using an integrated system of a confocal microscope and an AFM with a tip-less cantilever. The contact area was measured by confocal microscope and quantified by image processing, then used to convert force to stress. The Young's modulus of T24 cells was determined directly from the slope of stress-strain curves as 0.88±0.12 kPa. In comparison, we also applied previous indentation method and contact mechanics model fitting (Hertz model, Kevin-Voigt model, Standard Linear Solid model, all with Hertzian contact assumptions). The results obtained through each model were 1.54±0.21 kPa, 2.30±0.448 kPa, 1.80±0.32 kPa, respectively (pairwise P<0.05); and the Young's modulus from the three models showed error of 78%±26%, 164%±50%, 105%±21%, compared with our direct stress-strain characterization of the same 10 cells.