In a paper published in PNAS this week, researchers at the Institute of Bioengineering of Catalonia (IBEC) in Barcelona have uncovered a crucial mechanism by which cells probe their environment, taking them a step closer to understanding how they interact with their surroundings; in turn, this opens doors to being able to predict or control cell behaviour.
Image: A cell spreading on the nanometric pillars
“How a cell measures rigidity has long been a mystery,” explains Pere Roca-Cusachs, senior researcher in IBEC’s Cellular and Respiratory Biomechanics group, which carried out the research alongside collaborators in the US. “Does it squeeze its environment with a given force, and then measure how much it moves, like a person bouncing on a bed to see how much it gives? Or, on the other hand, does it apply a given distortion, and then measure how much force is needed? Also, is the measurement done by the cell as a whole, or does it have multiple miniature sensors which probe the rigidity at various different sites?”
To answer these questions, the scientists placed cells on a bed of flexible nanometric pillars. “By tracking the movement of these pillars, we were able to map how cells exert forces on their environment with a resolution never achieved before,” explains Pere. “Using this technique, we found that the rigidity sensor in cells is a small complex of not more than one micrometre (1/1000th of a millimetre) long.” The researchers saw, too, that the cell does indeed possess multiple copies of this complex, all of which apply a constant displacement of 60 nanometers – less than 1/10000th of a millimeter. The sensors then measure the applied force to deduce the rigidity of the environment.
“These findings represent a very important step towards understanding how cells interact with their environment, knowledge which is crucial to fabricate organs like lungs or hearts in vitro or treat diseases such as cancer,” says Pere.
Reference article: Ghassemi, S., Meacci, G., Liu, S., Gondarenko, A.A., Mathur, A., Roca-Cusachs, P., Sheetz, M.P., and Hone, J. (2012). Cells test substrate rigidity by local contractions on sub-micrometer pillars. PNAS, in press.