Molecular Engineering of Stem Cell Surfaces Via Biomembrane Fusion Transfer From Proteolipobead/Matrix Hybrid Materials

The presentation of ligands to stem cells in order to recreate the complex 3-D microenvironment of the stem cell niche is a major challenge in biomaterials. The overall aim of our effort is to test the hypothesis that the introduction of biomembrane- microsphere assemblies into 3D scaffolds is a viable biomimetic means to present ligands/bound factors to stem cells and mimic cellular communication in the stem cell niche. We have developed a new platform to present molecules to stem cells within a biomimetic architecture: as laterally-mobile molecules embedded in the context of a tailored biomembrane structure (protetolipobead: PLB) . Confocal microscopy studies were conducted to visualize proteolipobead-displayed N-cadherin engaged in interactions with human mesenchymal stem cells (MSCs) in situ, from 3D CLSM reconstruction of hMSCs in N-cadherin proteolipobead/Collagen-I 3D constructs. In a fraction of the MSCs interacting with the PLBs, images consistent with PLB-to-MSC biomembrane fusion were evidenced. In essence, molecular engineering of the MSC surface was evidenced where N-Cadherin from the engineered PLBs diffused onto the surface of live MSCs. This work constitutes a new method for introducing a wide range of complex membrane proteins and signaling molecules to live cells without genetic manipulation. We present further investigations of this fusion phenomenon under a range of conditions and surface characteristics of the PLB substrates.