Aggregation of Oligoarginines at Phospholipid Membranes: Molecular Dynamics Simulations, Time-Dependent Fluorescence Shift, and Biomimetic Colorimetric Assays

作者：Vazdar Mario^*; Wernersson Erik; Khabiri Morteza; Cwiklik Lukasz; Jurkiewicz Piotr; Hof Martin; Mann Ella; Kolusheva Sofiya; Jelinek Raz; Jungwirth Pavel

来源：Journal of Physical Chemistry B, 2013, 117(39): 11530-11540.

DOI：10.1021/jp405451e

A 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 10 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.

• 出版日期2013-10-3