Uniaxial strain system to investigate strain rate regulation in vitro

Cells are able to sense and respond to mechanical strain both in vivo and in vitro, and though the ability of strain to stimulate intracellular biochemical events is well established, the influence of the rate at which these strains are applied has not been extensively investigated. In order to study the role of strain as well as strain rate, an in vitro device has been developed and validated for applying cyclic uniaxial strains to cells cultured on a silicone sheet substrate. The stepper motor driven system provides strains up to 50% in increments as small as 12 nm (0.25 mu strain) at strain rates from mu strain/day to 300%/s. Computer control allows all displacement parameters to be easily modified and provides precise control, while the low profile design and planar culture surface allows the cells to be visualized during all phases of cell culture and strain application. Displacement parameters were verified using a linear variable displacement transformer to track linear motion, while strain analysis of the membrane deformation revealed a relatively homogeneous strain field across the culture wells. As a demonstration of both the device capability and the ability of strain rate to actively modulate the cellular response, the strain rate dependence of protein synthesis was investigated in C2C12 skeletal muscle myotube cultures subjected to cyclic uniaxial strain of 7% at strain rates ranging from 1.4% to 70% s(-1). Protein synthesis rates displayed a biphasic response, with increased protein synthesis at strain rates up to 25% s(-1), and a peak synthesis rate of 135% of control. The uniaxial strain system described provides a high performance and versatile platform with which to study the role of mechanical strain in a variety of cells and tissues. (C) 2001 American Institute of Physics.