Document Detail


Fundamental molecular mechanism for the cellular uptake of guanidinium-rich molecules.
MedLine Citation:
PMID:  25405895     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Guanidinium-rich molecules, such as cell-penetrating peptides, efficiently enter living cells in a non-endocytic energy-independent manner transporting a wide range of cargos, including drugs and biomarkers. The mechanism by which these highly cationic molecules efficiently cross the hydrophobic barrier imposed by the plasma membrane remains a fundamental open question. Here, a combination of computational, in vitro and live cell experimental evidence reveals an efficient energy-independent translocation mechanism for arginine-rich molecules. This mechanism unveils the essential role of guanidinium groups and two universal cell components: fatty acids and the cell membrane pH gradient. Deprotonated fatty acids in contact with the cell exterior interact with guanidinium groups leading to a transient membrane channel that facilitates the transport of arginine rich peptides towards the interior of cells. In the cytosolic side, fatty acids become protonated releasing the peptides and resealing the channel. This fundamental mechanism appears to be universal across cells from different species and kingdoms.
Authors:
Henry D Herce; Angel E Garcia; M Cristina Cardoso
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-18
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  -     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-18     Completed Date:  -     Revised Date:  2014-11-19    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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