Contributions of Lipid Bilayer Hosts to Structure and Activity of Multifunctional Supramolecular Guests

Abstract

The question of whether or not the surrounding lipid bilayer host contributes to structure and activity of included functional guests is a general topic of current scientific concern. We report that synthetic multifunctional pores are of use to address this elusive question, because the detection of their catalytic activity is membrane independent. According to their salt-rate profiles, unstable multifunctional supramolecules with permanent internal charges show highest membrane sensitivity, and the dependence of membrane sensitivity on the acidity of internal cations exceeds that on supramolecule stability. These results can, with all appropriate caution, be interpreted as indications for the existence of long-range EMP-ICR interactions (EMP: external membrane pressure, ICR: internal charge repulsion) between membrane hosts and functional guests that can, for instance, prevent the 'explosion' and promote the 'implosion' of over- and undercharged transmembrane barrel-stave supramolecules, respectively.

Translocation of Hydrophilic Molecules across Lipid Bilayers by Salt-Bridged Oligocholates

“…To keep the pore open, the structure must be able to withstand the external membrane pressure when incorporated into a bilayer. 22 Despite the significant efforts devoted to synthetic nanopores, limited designs exist currently. An early example was Ghadiri's cyclic D/L-peptides, which self-assembled into transmembrane pores large enough for glucose and glutamic acid to pass through.…”

Molecular Recognition by Synthetic Multifunctional Pores in Practice: Are Structural Studies Really Helpful?

“…[3,23] 2) The surrounding bilayer is not just a hydrophobic solvent, but a supramolecular host that is part of the suprastructure of the included multifunctional guest. [3,12,30,31] 3) The active synthetic multifunctional pore 2-9 is often formed by a small fraction of the added rod 1. A major fraction remains in an unknown inactive form that is not relevant for function but detected exclusively by conventional methods for structure determination.…”

Controlling supramolecular polymerization through multicomponent self‐assembly

“…Due to the spacial proximity and electrostatic repulsion of the multiply charged bases or acids in these synthetic pores, the intrinsic pK a of the base/acid is shifted, an observation which the authors described using the intermediate internal charge repulsion (ICR) model. 312,313 Lack of ICR was suggested to account for "implosion," low ICR for contraction, high ICR for expansion, and excess ICR for "explosion" of the b-barrels pores. Contributions of the surrounding bilayer also had to be taken into account: the external membrane pressure (EMP) model was suggested to protect the overcharged barrels from exploding and to promote the implosion of undercharged barrels, 312,313 an effect that has important consequences for the catalytic activity of the synthetic pores.…”

“…Contributions of the surrounding bilayer also had to be taken into account: the external membrane pressure (EMP) model was suggested to protect the overcharged barrels from exploding and to promote the implosion of undercharged barrels, 312,313 an effect that has important consequences for the catalytic activity of the synthetic pores. 313 Interestingly the balance of attractive and repulsive features that is described by the ICR model for these barrel-stave supramolecules is not too dissimilar to the frustrated type self-assembly that was introduced in the case of supramolecular polymerizations into 1-D nanorods. The Besenius lab has shown that in the case of the homopolymerization of polyanionic dendritic peptides the attractive supramolecular interactions are opposed by repulsive electrostatic interactions at neutral pH and low ionic strength.…”