Tyrosine-Derived Polymeric Surfactants Modulate the Fusion of Normal and Cancer Cells

Abstract

Plasma membrane fusion and resealing play essential roles in diverse biological processes, including embryogenesis, morphogenesis, tissue repair, and cancer metastasis. Certain polymeric surfactants, including poly(ethylene glycol) (PEG) and triblock poly(alkylene oxides) like Poloxamer 188 (P188), are known to modify cell membrane biophysical properties. This has enabled applications such as PEG fusion for severed nerves and P188-mediated muscle tissue repair. Similar to P188, tyrosine-derived triblock copolymers (TyPS) form self-assembled nanospheres that can reversibly insert into phospholipid monolayers and cell plasma membranes. The effects of phospholipid head group polarity on the insertion of TyPS into Langmuir phospholipid monolayers are examined here. The hydrophobic blocks of the polymeric surfactants are found to provide the primary driving force for insertion in the phospholipid membranes. The impact of the TyPS, PEG, and P188, alone and in combination, on membrane fusion in normal (L929 mouse fibroblast) and transformed (MDA-MB-231 human breast cancer) cells is then determined using in vitro cell culture methods. The cell culture studies demonstrate that PEG induces fusion in both cell lines and reveal that the combination of PEG and P188 has a strong positive synergistic effect on cell fusion. In contrast, the TyPS exhibits strong anti-fusion properties, inhibiting both spontaneous and PEG-enhanced fusion. P188 has a weak antifusion effect compared to TyPS. The fusogenic or antifusogenic behaviors of the polymeric surfactants correlate with their thermodynamic Hansen solubility parameters, and the synthetic tunability of the TyPS enables access to a far greater range of hydrophobicities than the available commercial Poloxamers. These findings suggest that mixtures of PEG and P188 may have the potential to enhance tissue repair and hybridoma output for monoclonal antibody production, while the TyPS may have the potential to inhibit metastatic cancers.