Surfaces mimicking glycosaminoglycans trigger different response of stem cells via distinct fibronectin adsorption and reorganization

We report on the utility of a platform created by self-assembled monolayers to investigate the influence of the degree of sulfation of glycosaminoglycans (GAGs) on their interactions with fibronectin (Fn) and the impact of these interactions on the adhesion and morphology of human adipose derived stem cells (ASCs). We used the label-free QCM-D, AFM and SPR to follow the changes in the protein adlayer in close proximity to the substrates surface and QCM-D in combination with live imaging to characterize the adherent cells. Our results suggest that Fn interactions with GAGs are governed by both H-bonding and electrostatic forces. Strong electrostatic interactions cause irreversible change in the protein conformation, while the weaker H-bonding only partially restricts the protein flexibility, allowing Fn reorganization and exposure of its binding sites for ASC adhesion. These findings imply that a delicate balance between these two types of forces must be considered in the design of biomaterials that mimic GAGs.We acknowledge EU for financial support (FP7/2007-2013, under Grants REGPOT-CT2012-316331-POLARIS and ERC- 2012-ADG-20120216-321266 for the project ComplexiTE). I.P. is thankful to the Portuguese Foundation for Science and Technology (IF/00032/2013). The authors are very grateful to Dr. Raquel Teixeira for her help with the treatment and discussion of the MP-SPR data