DNA modified MSN-films as versatile biointerfaces to study stem cell adhesion processes

Abstract

A significant bottleneck in the clinical translation of stem cells remains eliciting the desired stem cell behavior once transplanted in the body. In their natural environment, stem cell fate is regulated by their interaction with extracellular matrix (ECM), mainly through integrin-mediated cell adhesion. 2D biointerfaces that selectively present ECM-derived ligands can be used as valuable tools to study and improve our understanding on how stem cells interact with their environment. Here we developed a new type of biointerface based on mesoporous silica nanoparticles (MSN) which are interesting nanomaterials for biointerface engineering because they allow close control over surface physiochemical properties. To create the platform, DNA functionalized MSN (MSN-ssDNA) with varying PEG linker length were developed. Cell adhesion tripeptide RGD was conjugated to a complementary DNA strand, which could specifically bind to MSN-ssDNA to create MSN-dsDNA-RGD films. We showed that MSN-dsDNA-RGD films could promote hMSCs adhesion and spreading, whereas MSN-dsDNA films without RGD resulted in poor cell spreading with round morphology, and low cell adhesion. In addition, we showed that cell adhesion to the films is PEG length-dependent. The design of the platform allows easy incorporation of other and multiple ECM ligands, as well as soluble cues, making MSN-ssDNA based biointerfaces a novel tool to study ligand–stem cell interactions.