Exploring the Molecular Dynamics of a Lipid-A Vesicle at the Atom Level: Morphology and Permeation Mechanism

Author(s)

Santos, Denys E. S. ; De Nicola, Antonio ; dos Santos, Vinicius F. ; Milano, Giuseppe ; Soares, Thereza A. A.

• Document type: Journal article
• Source: Journal of Physical Chemistry B; v. 127, n. 30, p. 9-pg., 2023-07-19.

Abstract

Lipid-A was previouslyshown to spontaneously aggregateinto avesicle via the hybrid particle field approach. Weassess the validity of the proposed vesiculation mechanism by simulatingthe resulting lipid-A vesicle at the atom level. The spatial confinementimposed by the vesicle geometry on the conformation and packing oflipid-A induces significant heterogeneity of physical properties inthe inner and outer leaflets. It also induces tighter molecular packingand lower acyl chain order compared to the lamellar arrangement. Around5% of water molecules passively permeates the vesicle membrane inwardand outward. The permeation is facilitated by interactions with watermolecules that are transported across the membrane by a network ofelectrostatic interactions with the hydrogen bond donors/acceptorsin the N-acetylglucosamine ring and upper regionof the acyl chains of lipid-A. The permeation process takes placeat low rates but still at higher frequencies than observed for thelamellar arrangement of lipid-A. These findings not only substantiatethe proposed lipid-A vesiculation mechanism but also reveal the complexstructural dynamics of an important nonlamellar arrangement of lipid-A. (AU)

• FAPESP's process: 21/04283-3 - A multi-resolution approach to cation-induced polymorphism of lipopolysaccharide aggregates
• Grantee: Thereza Amélia Soares da Silva
• Support Opportunities: Regular Research Grants