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Molecules 2014, 19(7), 9228-9239; https://doi.org/10.3390/molecules19079228

Mechanistic Insight into CM18-Tat11 Peptide Membrane-Perturbing Action by Whole-Cell Patch-Clamp Recording

1
Dipartimento di Scienze della Vita e Biotecnologie, Università di Ferrara, Via L. Borsari 46, I-44100 Ferrara, Italy
2
NEST, Scuola Normale Superiore and Istituto Nanoscienze-CNR, Piazza San Silvestro 12 - 56127 Pisa, Italy
3
Center for Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia, Piazza San Silvestro 12 - 56127 Pisa, Italy
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 30 April 2014 / Revised: 25 June 2014 / Accepted: 30 June 2014 / Published: 2 July 2014
(This article belongs to the Special Issue Peptide Chemistry)
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Abstract

The membrane-destabilization properties of the recently-introduced endosomolytic CM18-Tat11 hybrid peptide (KWKLFKKIGAVLKVLTTG-YGRKKRRQRRR, residues 1–7 of cecropin-A, 2–12 of melittin, and 47–57 of HIV-1 Tat protein) are investigated in CHO-K1 cells by using the whole-cell configuration of the patch-clamp technique. CM18-Tat11, CM18, and Tat11 peptides are administered to the cell membrane with a computer-controlled micro-perfusion system. CM18-Tat11 induces irreversible cell-membrane permeabilization at concentrations (≥4 µM) at which CM18 triggers transient pore formation, and Tat11 does not affect membrane integrity. We argue that the addition of the Tat11 module to CM18 is able to trigger a shift in the mechanism of membrane destabilization from “toroidal” to “carpet”, promoting a detergent-like membrane disruption. Collectively, these results rationalize previous observations on CM18-Tat11 delivery properties that we believe can guide the engineering of new modular peptides tailored to specific cargo-delivery applications. View Full-Text
Keywords: CPP; AMP; chimera; patch-clamp; toroidal-pore; carpet CPP; AMP; chimera; patch-clamp; toroidal-pore; carpet
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This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Fasoli, A.; Salomone, F.; Benedusi, M.; Boccardi, C.; Rispoli, G.; Beltram, F.; Cardarelli, F. Mechanistic Insight into CM18-Tat11 Peptide Membrane-Perturbing Action by Whole-Cell Patch-Clamp Recording. Molecules 2014, 19, 9228-9239.

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