Directing Cellular Fate Through Water-Soluble Membrane Proteins

The potential of water-soluble membrane proteins (wsMPs) has not been realized fully. The wsMPs have nearly identical functions as to their membrane-bound counterparts. In this article we improve our methodology to create water-soluble receptors to alter cellular fate. Frizzled receptors are part of the Wnt signaling pathway. Wnt-activated Frizzled receptors activate transcription factor β-catenin that affect cell growth, proliferation and epigenetic phenotypes that are well established in cellular models. Treating human embryonic kidney cells (HEK 293) with wsFrizzled receptors changes the cells fate in a fashion similar to that of chemically (CHIR99021) activated Wnt pathway. We present three examples where wsMPs are functional in dictating cellular fate, both in vitro and in vivo. We call this method in vivo deployment of recombinant viable IMPs: iDRIVE. Future work will employ wsMPs to differentiate stem cells in the production of research and clinically relevant organoids.