Time-dependent fluorescence shift method, biomimetic colorimetric assays, and molecular
dynamics simulations have been performed in search of explanations why arginine rich
peptides with intermediate lengths of about ten amino acids translocate well through cellular
membranes, while analogous lysine rich peptides do not. First, we demonstrate that an
important factor for efficient peptide adsorption, as the first prerequisite for translocation
across the membrane, is the presence of negatively charged phospholipids in the bilayer.
Second, we observe a strong tendency of adsorbed arginine (but not lysine) containing
peptides to aggregate at the bilayer surface. We suggest that this aggregation of oligoarginines
leads to partial disruption of the bilayer integrity due to the accumulated large positive charge
at its surface which increases membrane-surface interactions due to the increased effective
charge of the aggregates. As a result, membrane penetration and translocation of medium
length oligoarginines becomes facilitated in comparison to single arginine and very long
polyarginines, as well as to lysine containing peptides.