Effects of Mechanical Stress on Calcium Transport in Cells of the Immune System

Rosey Whiting, Boise State University
Daniel Fologea, Boise State University

This special issue is Supplement 1 of the Biophysical Journal.


Immune cells are subjected to extreme mechanical perturbation in both normal and pathophysiological circumstances, leading to the need for a better understanding of the role played by mechano-transduction in the immune response. In this endeavor, we focused on the mechano-sensitive TRPV4 channel. This Ca2+transporter is expressed in monocytes, macrophages, T-cells, and neutrophils and is implicated in pro-inflammatory cascades within a variety of tissues. This research aims to investigate the activation of TRPV4 in immune cells (RAW264.7 macrophages and Jurkat T lymphocytes) upon mechanical stress achieved either by osmotic stress or stretch of a support membrane the cells are grown on. Ca2+influx upon channel activation is assessed by employing Ca2+sensitive dyes, fluorescence spectroscopy and fluorescence microscopy. The hypothesis that Ca2+is transported through TRPV4 channels is confirmed by experiments in which we used specific TRPV4 channel inhibitors added to the bulk medium before exerting the mechanical stress. Our work leads to the conclusion that mechanical stress applied to the cell membrane activates the TRPV4 channels and the consequent Ca2+transport, which may have implications for a better understanding of how mechanical stress may modulate the immune response. In addition, these results indicate a potential link between microgravity and alterations of immune system function, which may constitute a serious risk factor for long space missions.