Instability of membranes containing ionizable cationic lipids: Effects of the repulsive range of headgroups and tail structures.
Colloids Surf B Biointerfaces
; 236: 113807, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38417348
ABSTRACT
The stability of membranes formed by ionizable cationic lipids, which constitute the primary components in lipid nanoparticles capable of endosomal escape, is explored using coarse-grained dissipative particle dynamics. Three types of ionizable model lipids with different tail structures are considered. Endosome acidification causes the ionization of lipids, leading to an increased repulsive range between their headgroups. When electrostatic repulsion is modeled as a conservative force with a long-range cutoff distance (rc,HH), the membrane and vesicle experience a loss of structural integrity and develop holes as rc,HH is beyond a critical value, which varies with the tail structure. When Coulombic repulsion is explicitly incorporated and intensified, a fully ionized lipid membrane undergoes a loss of structural integrity, displaying a qualitative similarity to the effect observed with the increase in rc,HH on the membrane stability. Qualitatively similar results are obtained for partially ionized membranes as the fraction of charged lipids increases. The stability of a mixed lipid membrane containing both ionizable and conventional lipids is also investigated. The disruption of the bilayer structure occurs for a sufficiently high charged fraction. The membrane instability can be attributed to the decrease in the packing parameter, which significantly deviates from unity as the interaction range increases.
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Base de dados:
MEDLINE
Assunto principal:
Nanopartículas
Idioma:
En
Revista:
Colloids Surf B Biointerfaces
Assunto da revista:
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article