Artículo
Adsorption and insertion of polyarginine peptides into membrane pores: the trade-off between electrostatics, acid-base chemistry and pore formation energy
Ramírez, Pedro Germán
; del Popolo, Mario Gabriel
; Vila, Jorge Alberto
; Szleifer, I.; Longo, Gabriel Sebastian
Fecha de publicación:
09/2019
Editorial:
Academic Press Inc Elsevier Science
Revista:
Journal of Colloid and Interface Science
ISSN:
0021-9797
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The mechanism that arginine-rich cell penetrating peptides (ARCPPs) use to translocate lipid membranes is not entirely understood. In the present work, we develop a molecular theory that allows to investigate the adsorption and insertion of ARCPPs on membranes bearing hydrophilic pores. This method accounts for size, shape, conformation, protonation state and charge distribution of the peptides; it also describes the state of protonation of acidic membrane lipids. We present a systematic investigation of the effect of pore size, peptide concentration and sequence length on the extent of peptide adsorption and insertion into the pores. We show that adsorption on the intact (non-porated) lipid membrane plays a key role on peptide translocation. For peptides shorter than nona-arginine, adsorption on the intact membrane increases significantly with chain length, but it saturates for longer peptides. However, this adsorption behavior only occurs at relatively low peptide concentrations; increasing peptide concentration favors adsorption of the shorter molecules. Adsorption of longer peptides increases the intact membrane negative charge as a result of further deprotonation of acidic lipids. Peptide insertion into the pores depends non-monotonically on pore radius, which reflects the short range nature of the effective membrane-peptide interactions. The size of the pore that promotes maximum adsorption depends on the peptide chain length. Peptide translocation is a thermally activated process, so we complement our thermodynamic approach with a simple kinetic model that allows to rationalize the ARCPPs translocation rate in terms of the free energy gain of adsorption, and the energy cost of creating a transmembrane pore with peptides in it. Our results indicate that strategies to improve translocation efficiency should focus on enhancing peptide adsorption.
Palabras clave:
CELL PENETRATING PEPTIDES
,
MOLECULAR MODELING
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Licencia
Identificadores
Colecciones
Articulos(ICB)
Articulos de INSTITUTO INTERDISCIPLINARIO DE CIENCIAS BASICAS
Articulos de INSTITUTO INTERDISCIPLINARIO DE CIENCIAS BASICAS
Articulos(IMASL)
Articulos de INST. DE MATEMATICA APLICADA DE SAN LUIS
Articulos de INST. DE MATEMATICA APLICADA DE SAN LUIS
Articulos(INIFTA)
Articulos de INST.DE INV.FISICOQUIMICAS TEORICAS Y APLIC.
Articulos de INST.DE INV.FISICOQUIMICAS TEORICAS Y APLIC.
Citación
Ramírez, Pedro Germán; del Popolo, Mario Gabriel; Vila, Jorge Alberto; Szleifer, I.; Longo, Gabriel Sebastian; Adsorption and insertion of polyarginine peptides into membrane pores: the trade-off between electrostatics, acid-base chemistry and pore formation energy; Academic Press Inc Elsevier Science; Journal of Colloid and Interface Science; 552; 9-2019; 701-711
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