Quantifying the Local Mechanical Properties of Cells in a Fibrous Three-Dimensional Microenvironment

Abstract

Measurements of the mechanical response of biological cells are critical for understanding injury and disease, for developing diagnostic tools, and for computational models in mechanobiology. Although it is well known that cells are sensitive to the topography of their microenvironment, the current paradigm in mechanical testing of adherent cells is mostly limited to specimens grown on flat two-dimensional substrates. In this study, we introduce a technique in which cellular indentation via optical trapping is performed on cells at a high spatial resolution to obtain their regional mechanical properties while they exist in a more favorable three-dimensional microenvironment. We combine our approach with nonlinear contact mechanics theory to consider the effects of a large deformation. This allows us to probe length scales that are relevant for obtaining overall cell stiffness values. The experimental results herein provide the hyperelastic material properties at both high ($100 s À1 ) and low ($1-10 s À1 ) strain rates of murine central nervous system glial cells. The limitations due to possible misalignment of the indenter in the three-dimensional space are examined using a computational model.

Engineered cell culture microenvironments for mechanobiology studies of brain neural cells

“…The particles become trapped at the beam focus if the optical forces are larger than the other acting forces. This technique has been used to trap silica beads to deform glial cell surfaces and measure their stiffness and elasticity ( Dagro et al, 2019 ). The main advantage of this technique is that it can be used in a 3D scaffold environment and measure forces in a 3D space ( Lenton et al, 2020 ).…”

Optical Tweezers Exploring Neuroscience

“…Amongst these methods, OT offers the advantage of being non-invasive, applying comparively large forces, being able to probe cells in a 3D scaffold environment and precisely measuring forces in 3D space (Nawaz et al, 2012;Capitanio and Pavone, 2013;Pontes et al, 2013;Arbore et al, 2019;Li et al, 2020). Very recently, Dagro et al (2019) used optically trapped silica beads to deform cell surfaces and measure their stiffness and elasticity. They successfully measured the elastic properties, at both high and low strain rates, of glial cells, opening a new avenue for the precise measurement of the mechanical properties of brain tissue.…”

Recent Advances on the Model, Measurement Technique, and Application of Single Cell Mechanics

“…E = σ/ε, the ratio of stress to strain. [7,17,18,38,39,43,48,69,70,[105][106][107]123,125,126,133,134,[139][140][141][142][143]149,152,155] Shear modulus (G)…”

“…After binding two small silicon beads on the cell membrane, he captured and stretched cells by applying calibrated tweezers so as to obtain the shear modulus of red blood cells (2.5 ± 0.4 µN/m). Muhammad et al [ 105 , 106 ] measured the local elasticity of cells by squeezing and stretching them with the indentation method, as shown in Figure 4 b. In addition, Muhammad [ 107 ] also used optical tweezers to explore the influence of the basal region on the hardness of cancer cells.…”

“… E = σ/ε, the ratio of stress to strain. [ 7 , 17 , 18 , 38 , 39 , 43 , 48 , 69 , 70 , 105 , 106 , 107 , 123 , 125 , 126 , 133 , 134 , 139 , 140 , 141 , 142 , 143 , 149 , 152 , 155 ] Shear modulus (G) Shear stress characterizes the material’s ability to resist shear strain. G = τ/γ, the ratio of shear stress to shear strain.…”