13/02/2017

Binding of the chemokine CXCL12α to its natural extracellular matrix ligand heparan sulfate enables myoblast adhesion and facilitates cell motility

Title: Binding of the chemokine CXCL12α to its natural extracellular matrix ligand heparan sulfate enables myoblast adhesion and facilitates cell motility
Authors:

Dhruv Thakar, Fabien Dalonneau, Elisa Migliorini, Hugues Lortat-Jacob, Didier Boturyn, Corinne Albiges-Rizo, Liliane Coche-Guerente, Catherine Picart and Ralf P. Richter

Journal: Biomaterials (2017) 123:24-38

The method is based on surfaces that reproduce selected aspects of the extracellular environment by displaying sugars and signalling molecules at tuneable densities and controlled orientation. The level of control with such tailor-made model surfaces is superior to what can be achieved in vivo and it thus becomes possible to study the response of cells to selected subsets of extracellular signals in exquisite detail. The researchers demonstrated that the presentation of the signalling protein CXCL12α through the GAG heparan sulfate is sufficient to promote the adhesion and spreading of muscle precursor cells (myoblasts). This finding adds a new facet to our understanding of cell adhesion, which was previously thought to require the engagement of cell adhesion receptors of the integrin family with proteins in the extracellular matrix. The researchers also showed that CXCL12α on heparan sulfate facilitates the motility of myoblasts, a process that is critical for cell migration and repair processes. The here-developed biomimetic surfaces thus hold promise for mechanistic studies of cellular responses to different presentations of biomolecules. They may be broadly applicable for dissecting the signalling pathways underlying receptor cross-talks, and thus may guide the development of novel biomaterials that promote highly specific cellular responses.
This work resulted from the Chair of Excellence Project “GAG2D”, a collaborative project between the Richter Lab and four research groups in Grenoble, funded by the Nanoscience Foundation (Grenoble, France).