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Membrane destabilizing properties of cell-penetrating peptides

Per Thorén (Institutionen för kemi- och bioteknik) ; D. Persson ; Per Lincoln (Institutionen för kemi- och bioteknik) ; Bengt Nordén (Institutionen för kemi- och bioteknik)
Biophysical Chemistry (03014622). Vol. 114 (2005), 2-3, p. 169-179.
[Artikel, refereegranskad vetenskaplig]

Although cell-penetrating peptides (CPPs), also denoted protein transduction domains (PTDs), have been widely used for intracellular delivery of large and hydrophilic molecules, the mechanism of uptake is still poorly understood. In a recent live cell study of the uptake of penetratin and tryptophan-containing analogues of Tat(48-60) and oligoarginine, denoted TatP59W, TatLysP59W and R7W, respectively, it was found that both endocytotic and non-endocytotic uptake pathways are involved [Thorén et al., Biochem. Biophys. Res. Commun. 307 (2003) 100-107]. Non-endocytotic uptake was only observed for the arginine-rich peptides TatP59W and R7W. In this paper, the interactions of penetratin, R7W, TatP59W and TatLysP59W with phospholipid vesicles are compared in the search for an understanding of the mechanisms for cellular uptake. While R7W, TatP59W and TatLysP59W are found to promote vesicle fusion, indicated by mixing of membrane components, penetratin merely induces vesicle aggregation. Studies of the leakage from dye-loaded vesicles indicate that none of the peptides forms membrane pores and that vesicle fusion is not accompanied by leakage of the aqueous contents of the vesicles. These observations are important for a proper interpretation of future experiments on the interactions of these peptides with model membranes. We suggest that the discovered variations in propensity to destabilize phospholipid bilayers between the peptides investigated, in some cases sufficient to induce fusion, may be related to their different cellular uptake properties.



Denna post skapades 2010-01-12.
CPL Pubid: 106540

 

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Institutioner (Chalmers)

Institutionen för kemi- och bioteknik (2005-2014)

Ämnesområden

Kemiteknik

Chalmers infrastruktur