Stereochemical Effect Revealed in Self-Assemblies Based on Archaeal Lipid Analogues Bearing a Central Five-Membered Carbocycle: A SAXS Study

The relative stereochemistry (cis or trans) of a 1,3-disubstituted cyclopentane unit in the middle of tetraether archaeal bipolar lipid analogues was found to have a dramatic influence on their supramolecular self-assembly properties. SAXS studies of two synthetic diastereomeric archaeal lipids bearing two lactosyl polar head groups at opposite ends revealed different lyotropic behaviors. The cis isomer led to L_c–L_α–Q_II transitions whereas the trans isomer retained an L_α phase from 20 to 100 °C. These main differences originate from the conformational equilibrium (pseudorotation) of 1,3-disubstituted cyclopentanes. Indeed, this pseudorotation exhibits quite similar orientations of the two substituents in a trans isomer whereas several orientations of the two alkyl chains are expected in a <i>cis</i>-1,3-dialkyl cyclopentane, thus authorizing more conformational flexibility in the lipid packing

Experimental Observation of Double-Walled Peptide Nanotubes and Monodispersity Modeling of the Number of Walls

Self-assembled nanoarchitectures based on biological molecules are attractive because of the simplicity and versatility of the building blocks. However, size control is still a challenge. This control is only possible when a given system is deeply understood. Such is the case with the lanreotide acetate, an octapeptide salt that spontaneously forms monodisperse nanotubes when dissolved into pure water. Following a structural approach, we have in the past demonstrated the possibility to tune the diameter of these nanotubes while keeping a strict monodispersity, either by chemical modification of one precise amino acid on the peptide sequence or by changing the size of the counterions. On the basis of these previous studies, we replaced monovalent counterions by divalent ones to vary the number of walls. Indeed, in the present work, we show that lanreotide associated with a divalent counterion forms double-walled nanotubes while keeping the average diameter constant. However, the strict monodispersity of the number of walls was unexpected. We propose that the divalent counterions create an adhesion force that can drive the wall packing. This adhesion force is counterbalanced by a mechanical one that is related to the stiffness of the peptide wall. By taking into account these two opposite forces, we have built a general model that fully explains why the lanreotide nanotubes formed with divalent counterions possess two walls and not more

Structural Role of Counterions Adsorbed on Self-Assembled Peptide Nanotubes

Among noncovalent forces, electrostatic ones are the strongest and possess a rather long-range action. For these reasons, charges and counterions play a prominent role in self-assembly processes in water and therefore in many biological systems. However, the complexity of the biological media often hinders a detailed understanding of all the electrostatic-related events. In this context, we have studied the role of charges and counterions in the self-assembly of lanreotide, a cationic octapeptide. This peptide spontaneously forms monodisperse nanotubes (NTs) above a critical concentration when solubilized in pure water. Free from any screening buffer, we assessed the interactions between the different peptide oligomers and counterions in solutions, above and below the critical assembly concentration. Our results provide explanations for the selection of a dimeric building block instead of a monomeric one. Indeed, the apparent charge of the dimers is lower than that of the monomers because of strong chemisorption. This phenomenon has two consequences: (i) the dimer–dimer interaction is less repulsive than the monomer–monomer one and (ii) the lowered charge of the dimeric building block weakens the electrostatic repulsion from the positively charged NT walls. Moreover, additional counterion condensation (physisorption) occurs on the NT wall. We furthermore show that the counterions interacting with the NTs play a structural role as they tune the NTs diameter. We demonstrate by a simple model that counterions adsorption sites located on the inner face of the NT walls are responsible for this size control