Self-Organization of Mobile, Polyelectrolytic Dendrons on Stable, Amphiphile-Based Spherical Surfaces

Abstract

Spherical surfaces bearing mobile, solvophilic chains are ubiquitous. These systems are found in nature in the form of biological cells bearing carbohydrate chains, or glycans, or in drug delivery systems such as vesicles bearing polyethylene glycol chains and carrying therapeutic molecules. The self-organization of the chains on the spherical surface dictates the stability and functionality of the latter and is determined by key factors such as the interchain, chain–surface interactions, excluded volume, concentration of the chains, and external environment. This study develops a fundamental understanding of how these factors control the organization of mobile, solvophilic chains while preserving the stability of the spherical surface. To that end, the study focuses on the organization of polyamidoamine dendrons on the surface of a dipalmitoylphosphatidylcholine-based vesicle. The excluded volume of the chains and the external environment are, respectively, controlled via the dendron generation and the pH. For acidic and basic pH environments, the dendrons are extended away from the surface. As a consequence, the vesicles are able to accommodate significantly higher concentration of dendrons on their surface without rupturing. For acidic pH, the dendrons change their conformation to avoid intermeshing. However for basic pH, the dendrons only change their conformation at extremely high concentrations due to excluded volume effects. These conformational changes are attributed to the number of protonated dendron residues that vary as a function of pH. The results from this study will advance diverse subdisciplines within cell biology, biomedicine, and pharmaceuticals.

A perspective on coarse-graining methodologies for biomolecules: resolving self-assembly over extended spatiotemporal scales

“…Self-assembly of lipids into bilayers and vesicles is computationally efficient and reproducible in the Martini framework (Sharma et al, 2015). The selforganization of polyelectrolytic dendron-grafted amphiphiles (Figure 3A) within a lipid vesicle bilayer and its implications on the stability of the vesicle under different pH has been demonstrated using the Martini model (Banerjee et al, 2021;Banerjee and Dutt, 2023b). Peptide aggregation (Figures 3B, C) is accurately captured as a function of the concentration (Guo et al, 2012;Mushnoori et al, 2018; Frontiers in Soft Matter frontiersin.org Mushnoori et al, 2023).…”

Multiscale, Multiresolution Coarse-Grained Model via a Hybrid Approach: Solvation, Structure, and Self-Assembly of Aromatic Tripeptides

“…Hence, the process of self-assembly is inherently multiscale. The extended dynamics underlying the self-assembly process can be captured using reduced models, such as coarse-grained (CG) representations of the molecules. − To that end, another study adopted the CG explicit solvent Martini model to resolve the mechanisms underlying the self-assembly of FFF. The study reported the spontaneous formation of solid core nanospheres and nanorods within which the peptides were predominantly antiparallel to each other.…”