Helical macromolecular programming

The architectural plans for helical structures are encoded within the monomeric building blocks from which they are assembled. To design future functional architectures, it is of fundamental importance to understand how helices and other chiral structures can be constructed from low molecular weight compounds and macromolecules. The most relevant parameters for controlling the architecture are the size, topology, stereochemistry, and shape of the building block. Through processes of self-organization, these parameters can be expressed at several hierarchical levels: molecular, macromolecular, nanomolecular and higher levels

Transfection Mediated by Gemini Surfactants: Engineered Escape from the Endosomal Compartment

The structure of the lipoplex formed from DNA and the sugar-based cationic gemini surfactant 1, which exhibits excellent transfection efficiency, has been investigated in the pH range 8.8-3.0 utilizing small-angle X-ray scattering (SAXS) and cryo-electron microscopy (cryo-TEM). Uniquely, three well-defined morphologies of the lipoplex were observed upon gradual acidification: a lamellar phase, a condensed lamellar phase, and an inverted hexagonal (H||) columnar phase. Using molecular modeling, we link the observed lipoplex morphologies and physical behavior to specific structural features in the individual surfactant, illuminating key factors in future surfactant design, viz., a spacer of six methylene groups, the presence of two nitrogens that can be protonated in the physiological pH range, two unsaturated alkyl tails, and hydrophilic sugar headgroups. Assuming that the mechanism of transfection by synthetic cationic surfactants involves endocytosis, we contend that the efficacy of gemini surfactant 1 as a gene delivery vehicle can be explained by the unprecedented observation of a pH-induced formation of the inverted hexagonal phase of the lipoplex in the endosomal pH range. This change in morphology leads to destabilization of the endosome through fusion of the lipoplex with the endosomal wall, resulting in release of DNA into the cytoplasm.