Abstract
There is a strong demand for nanoindentation methods to probe the heterogeneous viscoelastic properties of soft tissues. Important applications include diagnosis of early onset diseases such as arthritis and investigations into cellular mechanoresponse in tissue. Quantification of tissue mechanics at length and time scales relevant to biological processes, however, remains a technical challenge. Here, we present a new nanoindentation approach that is ideally suited to probe the viscoelastic properties of soft, hydrated tissues. We built a ferrule-top probe that uses wavelength modulation in a Fabry-Pérot cavity configuration to detect cantilever deflection and to drive a feedback-controlled piezoelectric actuator. This technique allows us to control the static load applied onto the sample using an all-optical mm-sized probe. We extract the local elastic and viscous moduli of the samples by superposing a small oscillatory load and recording the indentation depth at the frequency of oscillation. By using a set of silicone elastomers with a range of stiffnesses representative of biological tissues, we demonstrate that the technique can accurately determine moduli over a wide range (0.1-100 kPa) and over a frequency range of 0.01-10 Hz. Direct comparison with macroscopic rheology measurements yields excellent quantitative agreement, without any fitting parameters. Finally, we show how this method can provide a spatially-resolved map of large variations in mechanical properties (orders of magnitude) across the surface of soft samples thanks to high sensitivity over large (>μm) cantilever deflections. This approach paves the way to investigations into the local dynamic mechanical properties of biological soft matter.
Highlights
There is a strong demand for nanoindentation methods to probe the heterogeneous viscoelastic properties of soft tissues
Paper moving through a circle, where the angle relative to the center scales linearly with probe displacement according to theory (eqn (3) and Fig. 3)
Calibration on a glass surface included this geometric effect and provided a check for the linearity between unwrapped angle and cantilever displacement. These results immediately demonstrate the strength of this approach: we can quantify cantilever deflection over 20 mm, a 100-fold increase relative to the linear approximation around quadrature
Summary
There is a strong demand for nanoindentation methods to probe the heterogeneous viscoelastic properties of soft tissues. We show how this method can provide a spatially-resolved map of large variations in mechanical properties (orders of magnitude) across the surface of soft samples thanks to high sensitivity over large (4mm) cantilever deflections This approach paves the way to investigations into the local dynamic mechanical properties of biological soft matter. Tissue mechanics has traditionally been probed by macroscopic mechanical tests such as stretching and shearing.[12] These tests have revealed interesting mechanical features such as strain-stiffening and active stiffness control by cells Since they average over large length scales, these methods cannot provide insight into the properties of the local niche surrounding the cells. Tissues are generally too stiff for this approach, since the force range available with thermal fluctuations or even optical and magnetic tweezers is too low to yield measurable deformations.[19]
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