Electrostatic effects in saturation of membrane binding of cationic cell-penetrating peptide
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ORIGINAL ARTICLE
Electrostatic effects in saturation of membrane binding of cationic cell‑penetrating peptide Anna Svirina1,2 · Ivan Terterov3 Received: 26 March 2020 / Revised: 17 August 2020 / Accepted: 7 November 2020 © European Biophysical Societies’ Association 2020
Abstract Membrane-active peptides that demonstrate cell-penetrating, antimicrobial or cytotoxic functions are diverse in their amino acid sequences, but share common physicochemical features like short length, amphipathic conformation in membrane environment and high net charge. Nonspecific electrostatic interactions of basic peptide residues with anionic membrane lipids play a crucial role in the initial binding of such peptides to plasma membranes of bacterial and mammalian cells. At the same time, a number of membrane-active peptides functions when they are localized at high concentrations on the lipid membranes. Dissecting the role of electrostatics in this functional peptide conditions is important to understand why the majority of them bear high positive charge. We have studied interaction of EB1 cell-penetrating peptide (charge + 8) with model anionic membranes. The saturation of peptide binding to liposomes that comprises 5%, 10% and 25% of negatively charged lipids (POPC/POPG mixture) was observed. We have found that peptide recharges liposomes and its surface saturating concentration increases with the amount of anionic lipids in a membrane so as a surface charge (bound peptide plus anionic lipids). This observation may be explained with the Gouy–Chapman theory based model with addition of independent effective peptide charges for peptide–peptide and peptide–lipid interactions, as well as steric saturation term. Additionally, in certain conditions, membrane bound peptide leads to liposome aggregation. In some lipid-to-peptide ratio regions disaggregation follows that may indicate an additional slow equilibration process after fast initial peptide binding. Keywords Cell-penetrating peptides · Membrane-active peptides · Charge saturation
Introduction Cell penetrating peptides (CPP) are short peptides, that are able to cross the membrane of the cell without any special receptors, and with a limited toxicity in their functional concentrations (Bechara and Sagan 2013). Combination of such properties make CPPs a promising class for development Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00249-020-01476-3) contains supplementary material, which is available to authorized users. * Anna Svirina [email protected] 1
Saint Petersburg Academic University, St. Petersburg, Russia
2
Present Address: B CUBE-Molecular Bioengineering, Dresden, Germany
3
Saint-Petersburg Clinical Scientific and Practical Center of Specialized Types of Medical Care (Oncological), St. Petersburg, Russia
of systems for drug delivery into cells. The first discovered CPPs were based on the shortest amino acid sequence necessary for the uptake of the HIV-1 Tat protein (Tat peptide) (Vives et al. 1997)
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