MALDI matrices used in this work contain carboxylic groups favouring protontransfer to the analyte, and thus the formation of protonated species. However, Cassady and coworkers nevertheless reported that peptides and proteins displayed good signals in the negative ion mode using acidic MALDI matrices. The compelling advantages of negative ion mode detection in high-mass MALDI-MS were also emphasized for homomeric protein complexes. This section aims at confirming previous measurements obtained on pure proteins with protein-protected metal nanoclusters and comparing the positive and negative mode MALDI-MS.