Cellular Strain Assessment Tool (CSAT): Precision Controlled Cyclic Uniaxial Tensile Loading

Abstract

Cells throughout our body are exposed to various forms of mechanical stimuli[1, 2]. To examine effects of mechanical cyclic strain on vascular cells, several types of strain devices have been developed, and the methods of force application range from use of dynamic indenters[3] to vacuum pressures (both positive[4] or negative[5, 6]) to stretch the bottom surface of the elastic substrate to which the cells are cultured. A number of custom uniaxial strain devices have been developed to examine cells that are normally exposed to lateral stresses[7–11]. However, a limitation to most uniaxial strain devices is that they can only accommodate a limited number of samples[8–12] at one time. Most devices also lack a platform to perform consistent clamping and loading of samples, which can significantly alter substrate strain[8, 9, 13] and ultimately, introduce large variations between experiments. Here we present a computer controlled precision strain application system composed of a custom multi-well uniaxial Cellular Strain Assessment Tool (CSAT) (Figure 1), a microscope adaptable mini CSAT, and custom elastomeric polydimethylsiloxane (PDMS) plates. The effect of cyclic tensile strain on the migration of endothelial cells was also analyzed in this study. Human umbilical vein endothelial cells (HUVECs), cultured in 2D directly on elastomeric polydimethylsiloxane (PDMS) substrates were exposed to cyclic tensile strain at physiologic levels, and demonstrated to enhance EC migration.

Cellular Orientation Is Guided by Strain Gradients

“…In the majority of cases, advancements in the field have been achieved by using simplified substrate strain fields (9-11, 13-16, 18). More recently, various other studies have employed ingeniously designed macro-devices with stretchable membranes that generate non-uniform strain amplitudes, both in the context of static and cycling stretching (8,(31)(32)(33)(34)(35)(36)(37)(38)(39). In a few cases (8,33,37), this approach allowed for the successful analysis of cell reorientation (among other responses) as a function of the strain amplitude over a single nonuniformly stretched membrane.…”

Directional Cell Migration Guided by a Strain Gradient

“…Non-uniform strain fields have been achieved using various approaches (23)(24)(25)(26)(27). In those works, it is consistently reported that cell reorientation is a function of strain magnitude and cells tend to avoid strain gradient and align perpendicular to the principal strain directions.…”