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How Cells Feel the Stretch

14.08.2014

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Top right: Before force is applied, cells grown in culture are randomly oriented. Top left: As a result of cyclic stretching, the cells organize in a uniform orientation. Bottom left: Following the cyclic stretching, cell skeletal fibers (“compressed springs,” red) align at the same angle as the cell body. Bottom right: Focal adhesions (green) at the ends of cellular skeleton fibers (red)

 
As our blood vessels pulsate with each heartbeat or our lungs inflate, the cells in these vessels and organs stretch as well. Such cells, which sense rhythmic fluctuations in force, have been found to neatly align at a very uniform angle. But how do they know in which direction to orient themselves? A new look at this process suggests that dozens of tiny individual adhesion sites at the cell’s outer edges collectively “steer” the entire cell so that it points in the right direction. These findings were recently published in Nature Communications.  
   
Observations in the last decade or two have revealed that cells can sense and respond to mechanical perturbations. When cells are repeatedly stretched together with an underlying substrate to which they adhere, they tend to align – more or less – in the direction they are stretched the least. For Dr. Ariel Livne in the lab of Prof. Benjamin Geiger in the Molecular Cell Biology Department, it was this “more or less” that was problematic. The researchers realized that something was missing from the models used to predict how a cell will behave when exposed to cyclic forces.
 
Cells that are being stretched may still hold on to the underlying surface through focal adhesions – “sticky” contact points around their edges. Running between the focal adhesions is a network of cellular skeleton fibers that effectively behave as “compressed springs.” Existing models for cell reorientation under cyclic stretching focused primarily on these springs, assuming they were the driving element behind a cell’s change of direction.
(l-r) Dr. Ariel Livne, Prof. Benjamin Geiger and Dr. Eran Bouchbiner
 
But Livne’s precise experiments and analysis showed that stretching the individual springs could not account for the observed cell orientations. In collaboration with Dr. Eran Bouchbinder of the Chemical Physics Department, a theoretician who studies the physics of complex systems, including the physical behavior of surfaces that experience forces, the team developed a theory to describe the responses of focal adhesions to alternating forces. This theory was highly successful at predicting not only the new direction in which cells realign, but also the rate of the entire rotation process. Thus the reorientation of the entire cell appears to begin at the “grass roots” through individual changes in the contact points at the cell edges. 
 
Prof. Benjamin Geiger’s research is supported by the Leona M. and Harry B. Helmsley Charitable Trust; the Adelis Foundation; the Fondazione Henry Krenter; Paul and Tina Gardner, Austin, TX; David and Molly Bloom, Canada; the estate of Anne S. Lubliner; the estate of Raymond Lapon; the estate of Alice Schwarz-Gardos; and the European Research Council. Prof Geiger is the incumbent of the Professor Erwin Neter Professorial Chair of Cell and Tumor Biology.
 

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