The planarian Schmidtea mediterranea as a model system for the discovery and characterization of cell‐penetrating peptides and bioportides

The Schmidtea mediterranea model system is a robust platform to assess the entry of cell‐penetrating peptides (CPPs) into a multi‐dimensional tissue. Transcription factors and other proteins, which regulate cellular differentiation in planaria, are also a source of highly efficient cationic CPP sequences. Eye regeneration is a simple and convenient assay by which to assess the impact of bioportides upon tissue morphogenesis.

Abstract

The general utility of the planarian Schmidtea mediterranea, an organism with remarkable regenerative capacity, was investigated as a convenient three‐dimensional model to analyse the import of cell‐penetrating peptides (CPPs) and bioportides (bioactive CPPs) into complex tissues. The unpigmented planarian blastema, 3 days post head amputation, is a robust platform to assess the penetration of red‐fluorescent CPPs into epithelial cells and deeper tissues. Three planarian proteins, Ovo, ZicA and Djeya, which collectively control head remodelling and eye regeneration following decapitation, are a convenient source of novel cationic CPP vectors. One example, Djeya1 (RKLAFRYRRIKELYNSYR), is a particularly efficient and seemingly inert CPP vector that could be further developed to assist the delivery of bioactive payloads across the plasma membrane of eukaryotic cells. Eye regeneration, following head amputation, was utilized in an effort to identify bioportides capable of influencing stem cell‐dependent morphogenesis. These investigations identified the tetradecapeptide mastoparan (INLKALAALAKKIL) as a bioportide able to influence the gross morphology of head development. We conclude that, compared with cellular monolayers, the S. mediterranea system provides many advantages and will support the identification of bioportides able to selectively modify the biology of totipotent neoblasts and, presumably, other mammalian stem cell types.

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