The way cells find their way around is by ‘groping’ rather than seeing their surroundings: this is the main conclusion of a study published in Nature last week involving several IBEC groups and their collaborators.
“We determined how cells detect the position of molecules (or ligands) in their environment with nanometric accuracy,” explains Pere Roca-Cusachs, group leader at IBEC and assistant professor at the University of Barcelona, who led the study. “By adhering to the ligands, the cells apply a force they can detect. As this force depends on the spatial distribution of the ligands, this allows the cells to ‘feel’ their surroundings. It’s like recognizing somebody’s face in the dark by touching it with your hand, rather than seeing the person.”
The interaction between cells and their ligands (or cellular microenvironment) is essential to maintain the function of any tissue. In fact, the detection of changes in the cellular environment is fundamental in any scenario where tissue remodeling occurs: embryonic development, wound healing, or tumor proliferation. Until now it was thought that cells somehow ‘measure’ distances, which led to the hypothesis that there must be some type of ‘standard’ molecule to help them do this. This work, which was supported by the ‘la Caixa’ Foundation, contradicts this.
The researchers also saw that “depending on the distribution of cellular forces, the activation of genetic transcription is affected – the phenomenon that determines which genes are expressed,” according to Roger Oria, first author of the study and a PhD student in Pere’s lab.
With this more integrated knowledge of how cells detect their surroundings, the researchers have found that by modifying the conditions of the cell environment (the rigidity and distribution of the ligands that make up the extracellular matrix), the adhesion response of the cell can be controlled, even as far as defining the range within in which the cell adheres at all.
This can be especially relevant in tumor processes, says Pere, given that we know that greater rigidity is related to the increased activation of oncogenes.
Oria R, Wiegand T, Escribano J, Elosegui-Artola A, Uriarte JJ, Moreno-Pulido C, Platzman I, Delcanale P, Albertazzi L, Navajas D, Trepat X, García-Aznar JM, Cavalcanti-Adam EA, Roca-Cusachs P. (2017). Force loading explains spatial sensing of ligands by cells. Nature, epub ahead of print
The work also involved researchers at the Instituto de Investigación en Ingeniería de Aragón of the University of Zaragoza and Germany’s Max Planck Institute for Medical Research and Heidelberg University. It was funded by the European Commission, MINECO, the Generalitat de Catalunya, the European Research Council, the “La Caixa” Foundation, La Marato de TV3 and the German Science Foundation (DFG).