A viewpoint now emerging is that a critical factor in lipid-mediated transfection (lipofection) is the structural evolution of lipoplexes upon Interaction with anionic cellular lipids, resulting in DNA release At the early stages of interaction, We found a universal behavior of lipoplex/anionic lipid (AL) Mixtures the lipoplex structure is slightly perturbed, while the one-dimensional DNA lattice between cationic membranes is largely diluted by ALs This finding is in excellent agreement with previous Suggestions on the mechanism of DNA unbinding from lipoplexes by ALs Upon further interaction, the propensity of a given lipoplex structure to be solubilized by anionic cellular lipids strongly depends on the shape coupling between lipoplex and ALs Furthermore. we investigated the effect of the membrane charge density and a general correlation resulted the higher the membrane charge density of anionic membranes, the higher their ability to solubilize the structure of lipoplexes and to promote DNA release Lastly, the fort-nation of nonlamellar phases in lipoplex/AL mixtures is regulated by the propensity of anionic cellular lipids to adopt nonlamellar phases Remarkably. also phase transition rates and [DNA release were found to be strongly affected by the shape coupling between lipoplex and ALs. It thus seems likely that the structural and phase evolution of lipoplexes may only be meaningful in the context of specific anionic cellular membranes These results highlight the phase properties of the carrier lipid/cellular lipid Mixtures as a decisive factor for optimal DNA release and suggest a potential strategy for the rational design of efficient cationic lipid carriers

Toward the Rational Design of Lipid Gene Vectors: Shape Coupling between Lipoplex and Anionic Cellular Lipids Controls the Phase Evolution of Lipoplexes and the Efficiency of DNA Release

MARCHINI, Cristina;MONTANI, Maura;AMICI, Augusto
2009-01-01

Abstract

A viewpoint now emerging is that a critical factor in lipid-mediated transfection (lipofection) is the structural evolution of lipoplexes upon Interaction with anionic cellular lipids, resulting in DNA release At the early stages of interaction, We found a universal behavior of lipoplex/anionic lipid (AL) Mixtures the lipoplex structure is slightly perturbed, while the one-dimensional DNA lattice between cationic membranes is largely diluted by ALs This finding is in excellent agreement with previous Suggestions on the mechanism of DNA unbinding from lipoplexes by ALs Upon further interaction, the propensity of a given lipoplex structure to be solubilized by anionic cellular lipids strongly depends on the shape coupling between lipoplex and ALs Furthermore. we investigated the effect of the membrane charge density and a general correlation resulted the higher the membrane charge density of anionic membranes, the higher their ability to solubilize the structure of lipoplexes and to promote DNA release Lastly, the fort-nation of nonlamellar phases in lipoplex/AL mixtures is regulated by the propensity of anionic cellular lipids to adopt nonlamellar phases Remarkably. also phase transition rates and [DNA release were found to be strongly affected by the shape coupling between lipoplex and ALs. It thus seems likely that the structural and phase evolution of lipoplexes may only be meaningful in the context of specific anionic cellular membranes These results highlight the phase properties of the carrier lipid/cellular lipid Mixtures as a decisive factor for optimal DNA release and suggest a potential strategy for the rational design of efficient cationic lipid carriers
2009
File in questo prodotto:
Non ci sono file associati a questo prodotto.

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: https://hdl.handle.net/11581/115120
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 48
  • ???jsp.display-item.citation.isi??? 47
social impact