Cells respond to their physical environment through calcium-regulated contractile fibers

The physical features of cellular environment are sensed by contractile bundles, called stress fibers. Researchers at the University of Helsinki found out that stress fibers are being regulated by a calcium-channel triggered signaling pathway inside the cell.

The force-producing bundles, composed of actin and myosin proteins, are the major mechanosensitive structures in most animal cells. Their formation is thus controlled by external forces applied to cells, and hence stress fibers assemble only in rigid environment, ensuring force-balance between the cell and its surroundings. Stress fibers are also critical for cells to respond to changes in their physical environment, but the molecular principles underlying mechanosensitive assembly of stress fibers have remained elusive.

Calcium-channels proved to be the solution

In a new study, researchers at the University of Helsinki discovered a signaling pathway that controls mechanosensitive assembly of stress fibers. They found that physical forces lead to a tension-sensitive opening of plasma membrane calcium-channels at the ends of stress fibers. The calcium influx then triggers a specific biochemical signaling pathway inside the cell to ensure proper assembly and maturation of contractile actomyosin bundles.

“These findings reveal how cells respond to changes in their physical environment, such as alterations in the stiffness of the extracellular matrix. Interestingly, many components of the mechanosensitive signaling pathway identified here are deregulated in various invasive cancers,” says Sari Tojkander, the lead author of this study.

Defects in reading and responding to the mechanical properties of the extracellular environment could thus play a major role in cancer progression.

“In the future, it will be interesting to examine how disruption of this mechanosensitive pathway contributes to cancer progression and whether it could be used as a therapeutic target,” highlights Tojkander.

Original article:

Tojkander S, Ciuba K, Lappalainen P (2018): CaMKK2 regulates mechanosensitive assembly of contractile actin stress fibers. Cell Reports, DOI: doi.org/10.1016/j.celrep.2018.06.011

Various biochemical signaling cascades control the differentiation, function, and morphology of cells. Besides chemical signaling, cells are also exposed to numerous physical cues that have an important role in guiding their morphogenesis, differentiation, and functions. Different tissues exhibit specific mechanical features that are critical in the maintenance of proper architecture and functions of the tissue.