Peptide-induced vesicle leakage is a common experimental test for the membrane-perturbing activity of antimicrobial peptides. The leakage kinetics is usually very slow, requiring minutes to hours for complete release of vesicle contents, and exhibits a biphasic behavior. We report here that, in the case of the peptaibol trichogin GA IV, all processes involved in peptide-membrane interaction, such as peptide-membrane association, peptide aggregation, and peptide translocation, take place on a timescale much shorter than the leakage kinetics. On the basis of these findings, we propose a stochastic model in which the leakage kinetics is determined by the discrete nature of a vesicle suspension: peptides are continuously exchanging among vesicles, producing significant fluctuations over time in the number of peptide molecules bound to each vesicle, and in the formation of pores. According to this model, the fast initial leakage is caused by vesicles that contain at least one pore after the peptides are randomly distributed among the liposomes, whereas the slower release is associated with the time needed to occasionally reach in an intact vesicle the critical number of bound peptides necessary for pore formation. Fluctuations due to peptide exchange among vesicles therefore represent the rate-limiting step of such a slow mechanism.

Mazzuca, C., Orioni, B., Coletta, M., Formaggio, F., Toniolo, C., Maulucci, G., et al. (2010). Fluctuations and the rate-limiting step of peptide-induced membrane leakage. BIOPHYSICAL JOURNAL, 99(6), 1791-1800 [10.1016/j.bpj.2010.07.010].

Fluctuations and the rate-limiting step of peptide-induced membrane leakage

MAZZUCA, CLAUDIA;COLETTA, MASSIMILIANO;PISPISA, BASILIO;VENANZI, MARIANO;STELLA, LORENZO
2010-09-22

Abstract

Peptide-induced vesicle leakage is a common experimental test for the membrane-perturbing activity of antimicrobial peptides. The leakage kinetics is usually very slow, requiring minutes to hours for complete release of vesicle contents, and exhibits a biphasic behavior. We report here that, in the case of the peptaibol trichogin GA IV, all processes involved in peptide-membrane interaction, such as peptide-membrane association, peptide aggregation, and peptide translocation, take place on a timescale much shorter than the leakage kinetics. On the basis of these findings, we propose a stochastic model in which the leakage kinetics is determined by the discrete nature of a vesicle suspension: peptides are continuously exchanging among vesicles, producing significant fluctuations over time in the number of peptide molecules bound to each vesicle, and in the formation of pores. According to this model, the fast initial leakage is caused by vesicles that contain at least one pore after the peptides are randomly distributed among the liposomes, whereas the slower release is associated with the time needed to occasionally reach in an intact vesicle the critical number of bound peptides necessary for pore formation. Fluctuations due to peptide exchange among vesicles therefore represent the rate-limiting step of such a slow mechanism.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore CHIM/02 - Chimica Fisica
Settore BIO/10
English
Con Impact Factor ISI
Kinetics; Unilamellar Liposomes; Antimicrobial Cationic Peptides; Stochastic Processes; Thermodynamics; Models, Biological; Amino Acid Sequence; Protein Transport; Cell Membrane
Mazzuca, C., Orioni, B., Coletta, M., Formaggio, F., Toniolo, C., Maulucci, G., et al. (2010). Fluctuations and the rate-limiting step of peptide-induced membrane leakage. BIOPHYSICAL JOURNAL, 99(6), 1791-1800 [10.1016/j.bpj.2010.07.010].
Mazzuca, C; Orioni, B; Coletta, M; Formaggio, F; Toniolo, C; Maulucci, G; De Spirito, M; Pispisa, B; Venanzi, M; Stella, L
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
BiophysJ2010Stella.pdf

accesso solo dalla rete interna

Licenza: Copyright dell'editore
Dimensione 210.61 kB
Formato Adobe PDF
210.61 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/11372
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 41
  • ???jsp.display-item.citation.isi??? 44
social impact