Cell-penetrating macromolecules: Direct penetration of amphipathic phospholipid polymers across plasma membrane of living cells

What is it about?

Nanoscaled materials are normally engulfed in endosomes by energy-dependent endocytosis and fail to access the cytosolic cell machinery. Although some biomolecules may penetrate non-endocytically or fuse with plasma membranes without overt membrane disruption, to date no synthetic macromolecule of comparable size has been shown to exhibit this property. Here, we discovered mechanism of direct cell membrane penetration using synthetic phospholipid polymers. These water-soluble amphiphilic phospholipid polymers enter the cytoplasm of living mammalian cells in vitro within a few minutes without overt bilayer disruption even under conditions where energy-dependent endocytic uptakes are blocked. Furthermore, targeted cytosolic distribution to cell organelles was achieved by selecting specific fluorescent tags to the polymers. Thus, the phospholipid polymers can provide a new way of thinking about access to the cellular interior, namely direct membrane penetration.

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