Cells sense their environment to explore it

“In this research we determined how cells detect the position of molecules (or ligands) in their surroundings, with a nanometre precision”, says Roca-Cusachs. “When the ligands join -he continues- cells apply a force they can detect. Since this force depends on the ligand spatial distribution, this enables cells to sense their surroundings. In some way, this would be the equivalent to recognizing someoneʼs face in the dark by touching the face with your hand, instead of seeing that person”. Interaction between cells and their ligands (or cell microenvironment) is essential to maintain the function of any tissue, and the detection of changes in the cell environment is in fact essential in all situations where there is tissue remodelling, such as the embryonic development, tumoral proliferation or the closing process of a wound.

In the study, researchers also saw how, “depending on this cell force distribution, it can affect the activation of genetic transcription, a phenomenon that determines which genes are expressed”, says Roger Oria, first author of the study and PhD student at the UB in Dr Roca-Cusachsʼ laboratory.

With this deeper knowledge of how cells detect their surroundings, researchers proved that by altering the conditions of the cellʼs environment (rigidity and distribution of those ligands that create the extracellular matrix) they can control the adherence response of the cell and they can even define a range in which the cell adheres, as well as the outside. This result, says Roca-Cusachs, can be certainly important in tumoral processes, since it is quite accepted for a greater rigidity to be related to a higher activation of oncogenes.

So far, researchers knew cells were able to perceive spatial and physical information at a nanoscale. In fact, it was thought for them to be able to “measure distances” and therefore people had hypotetized about the existence of some pattern molecule that could help in this process. According to the IBEC-UB researcher, this study opposes this hypothesis, since it shows that cells sense their surroundings more rather than seeing them.

In order to carry the research out, researchers developed some low-rigidity gel substrates to which a pattern of gold nanospheres covered by a protein are adhered, and which can control its separation. The cell recognizes these nanospheres as a ligand and therefore researchers can measure how cells regulate force distribution and the number of ligands to which they adhere regarding their density.

This study has the collaboration of the Aragon Institute of Engineering Research, the University of Zaragoza, the Max Planck Institute and Heidelberg University (Germany).

This study has been funded by the European Commission, the Spanish Ministry of Economy and Competitiveness, Generalitat de Catalunya, the European Research Council, “la Caixa” Bank Foundation, la Marató de Tv3 Foundation, and the German Science Foundation.


Article reference:
Roger Oria, Tina Wiegand, Jorge Escribano, Alberto Elosegui-Artola, Juan Jose Uriarte, Cristian Moreno-Pulido, Ilia Platzman, Pietro Delcanale, Lorenzo Albertazzi, Daniel Navajas, Xavier Trepat, José Manuel García-Aznar, Elisabetta Ada Cavalcanti-Adam i Pere Roca-Cusachs. “Force loading explains spatial sensing of ligands by cells”. Nature, December 2017. Doi:10.1038/nature24662