Microrheology of Human Lung Epithelial Cells Measured by Atomic Force Microscopy

Abstract

Lung epithelial cells are subjected to large cyclic forces from breathing. However, their response to dynamic stresses is poorly defined. We measured the complex shear modulus (G(*)(omega)) of human alveolar (A549) and bronchial (BEAS-2B) epithelial cells over three frequency decades (0.1-100 Hz) and at different loading forces (0.1-0.9 nN) with atomic force microscopy. G(*)(omega) was computed by correcting force-indentation oscillatory data for the tip-cell contact geometry and for the hydrodynamic viscous drag. Both cell types displayed similar viscoelastic properties. The storage modulus G'(omega) increased with frequency following a power law with exponent approximately 0.2. The loss modulus G"(omega) was approximately 2/3 lower and increased similarly to G'(omega) up to approximately 10 Hz, but exhibited a steeper rise at higher frequencies. The cells showed a weak force dependence of G'(omega) and G"(omega). G(*)(omega) conformed to the power-law model with a structural damping coefficient of approximately 0.3, indicating a coupling of elastic and dissipative processes within the cell. Power-law behavior implies a continuum distribution of stress relaxation time constants. This complex dynamics is consistent with the rheology of soft glassy materials close to a glass transition, thereby suggesting that structural disorder and metastability may be fundamental features of cell architecture.

Measuring Cell Viscoelastic Properties Using a Microfluidic Extensional Flow Device

“…One choice of model to capture viscoelastic behavior is the simple two-parameter power law for a time-dependent cell stiffness. This phenomenologic law has been shown to describe cell mechanical behavior for several cell types over a wide range of timescales as measured by several techniques, including optical magnetic twisting cytometry (39,40), atomic force microscopy indentation (41), and microfluidic constriction channel traversal (17). The power law can be expressed mathematically as (39)…”

Multiple‐Particle Tracking and Two‐Point Microrheology in Cells

“…In the active approach, a known force (or deformation) is applied to the material, and the resulting deformation (or force) is measured. In the cell rheology context, this usually relies upon atomic force microscope (AFM) (Alcaraz, 2003) or similar, force calibrated micro-cantilever instruments (Desprat, 2005). The passive approach, which is our focus in this chapter, examines the Brownian motion of tracers embedded in the soft material.…”

“…In reality, however, the rheological responses of cells measured to date have not contained identifiable molecular timescales and have not been satisfactorily reproduced by any biopolymer gel model yet studied. Several recent experiments have found the (low frequency) shear modulus of cells to be well described by a weak power-law form, G*(ω)~ω β , with reported values of β varying over the range 0.1-0.3 (Yamada, 2000;Fabry, 2001;Alcaraz, 2003;Lenormand, 2004;Desprat, 2005;. Such a power-law form has no characteristic times at all.…”

An historical perspective on cell mechanics

“…Although the main mechanical indicator is taken to be elasticity, rheological parameters have also been extracted from living cells using various approaches [129][130][131]. Indentation approaches have been used in conjunction with scanning to produce force maps [41][42][43][44]132] or in single spots on living cells to measure time dependence [125,127].…”