期刊
CHEMBIOCHEM
卷 23, 期 15, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.202200192
关键词
cell-penetrating peptides; dynamic acidity; early endosomes; pH gradients; trackers; transmembrane translocation
资金
- University of Geneva [200020 204175, 51NF40-185898, 51NF40-182895]
- National Centre Chemical Biology (NCCR) Chemical Biology [200020 204175, 51NF40-185898, 51NF40-182895]
- NCCR Molecular Systems Engineering [200020 204175, 51NF40-185898, 51NF40-182895]
- Swiss NSF [200020 204175, 51NF40-185898, 51NF40-182895]
- Universite de Geneve
- Swiss National Science Foundation (SNF) [200020_204175, 51NF40-182895, 51NF40-185898] Funding Source: Swiss National Science Foundation (SNF)
This study reveals that primary ammonium cations with higher pK(a) efficiently label early endosomes and Golgi networks. Guanidinium cations with higher pK(a) selectively label the plasma membrane in endocytosis. It is also found that guanidinium cations can self-assemble into micelles and penetrate mitochondria unidirectionally.
Labeled ammonium cations with pK(a)similar to 7.4 accumulate in acidic organelles because they can be neutralized transiently to cross the membrane at cytosolic pH 7.2 but not at their internal pHK(a) 9.8. We report here that primary ammonium cations with higher pK(a) 10.6, label early endosomes more efficiently. This maximized early endosome tracking coincides with increasing labeling of Golgi networks with similarly weak internal acidity. Guanidinium cations with pK(a) 13.5 cannot cross the plasma membrane in monomeric form and label the plasma membrane with selectivity for vesicles embarking into endocytosis. Self-assembled into micelles, guanidinium cations enter cells like arginine-rich cell-penetrating peptides and, driven by their membrane potential, penetrate mitochondria unidirectionally despite their high inner pH. The resulting tracking rules with an approximated dynamic range of pK(a) change similar to 3.5 are expected to be generally valid, thus enabling the design of chemistry tools for biology research in the broadest sense. From a practical point of view, most relevant are two complementary fluorescent flipper probes that can be used to image the mechanics at the very beginning of endocytosis.
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