Intravesicular and intervesicular interaction by orthogonal multivalent host–guest and metal–ligand complexation

Abstract

Host vesicles composed of amphiphilic ␤-cyclodextrin CD1 recognize metal-coordination complexes of the adamantyl-functionalized ethylenediamine ligand L via hydrophobic inclusion in the ␤-cyclodextrin cavities at the vesicle surface. In the case of Cu(II) and L, the resulting coordination complex was exclusively CuL2, and the interaction with the host vesicles was intravesicular, unless the concentration of metal complex and vesicles was high (>0.1 mM). In the case of Ni(II) and L, a mixture was formed consisting of mainly NiL and NiL2, the interaction with the host vesicles was effectively intervesicular, and addition of the guest-metal complex resulted in aggregation of the vesicles into dense, multilamellar clusters even in dilute solution [1 M Ni(II)]. The metal-L complex could be eliminated by a strong chelator such as EDTA, and the intervesicular interaction could be suppressed by a competitor such as unmodified ␤-cyclodextrin. The result from this investigation is that the strongest metal-coordination complex [Cu(II) with L] binds exclusively intravesicularly, whereas the weakest metal-coordination complex [Ni(II) with L] binds predominantly intervesicularly and is the strongest interfacial binder. These experimental observations are confirmed by a thermodynamic model that describes multivalent orthogonal interactions at interfaces.self-assembly ͉ vesicles ͉ cyclodextrins M ultivalent, noncovalent interactions at the interface of cell membranes are involved in a variety of biological processes such as cell-cell signaling, pathogen identification, and inflammatory response (1). Multivalent binding events have collective properties that are qualitatively and quantitatively different from the contributing monovalent interactions. For example, multivalent interactions lead to higher binding affinities and can afford larger contact areas between surfaces (1-3). Multivalency can be conveniently described by an effective concentration (C eff ) term that represents a probability of interaction between two interlinked reactive or complementary entities and symbolizes the concentration of one of the reacting or interacting functionalities as experienced by its counterpart (4, 5). Versatile model systems to investigate multivalent noncovalent interactions at the dynamic interface between cell membranes and the surrounding aqueous solution include self-assembled monolayers (SAMs) (6-11), nanoparticles (12-14), solid-supported lipid bilayers (15, 16), and bilayer vesicles (17-19).Metal-ligand coordination has been exploited to generate complex molecular architectures with specific topology, high stability, and original properties in aqueous solution (16,20,21). The N-nitrilotriacetic acid-histidine interaction is particularly interesting in a biological context. N-nitrilotriacetic acidfunctionalized lipids (22, 23) and SAMs (24, 25) have been used to immobilize proteins through multivalent interactions. In a comparable approach, the multivalent binding of Cu(II) ions to a membrane-bound dansyl-ethylenediamine conjugat...

Gender-Specific Hierarchy in Nuage Localization of PIWI-Interacting RNA Factors in Drosophila

“…The Ago3–piRNA complex, in turn, cleaves antisense transcripts of transposons and the resultant piRNAs are loaded onto Aub. Other factors required for the amplification loop include Vasa, Tudor (Tud), Krimp, Spn-E, and Mael (Findley et al, 2003; Lim and Kai, 2007; Malone et al, 2009). …”

“…Spn-E has a Tud domain (Gillespie and Berg, 1995; Ponting, 1997); however, it does not seem to associate with Aub and Ago3 (Nishida et al, 2009). Krimp also contains a Tud domain (Lim and Kai, 2007). Whether Krimp has the ability to associate with PIWI members through their sDMAs remains undetermined.…”

“…Hence, both nuage and Yb bodies are considered to be the locations for piRNA biogenesis (Findley et al, 2003; Lim and Kai, 2007; Olivieri et al, 2010; Saito et al, 2010; Qi et al, 2011; for review see Siomi et al, 2011). Zuc is localized to mitochondria (Olivieri et al, 2010; Saito et al, 2010).…”

Orthogonal switching of a single supramolecular complex

“…In particular, azobenzene derivatives have been extensively used as guests to form inclusion complexes with asymmetric macrocyclic hosts achieving binary photochemical devices [12][13][14][15][16][17] , based on its well-documented photoisomerism 18 . Although symmetric macrocyclic hosts such as cucurbit[n]urils, (n ¼ 7 and 8) have been used to form either binary inclusion complexes with CB [7] 19,20 , or ternary complexes with CB [8] and methylviologen (MV 2 þ ) 21 , no photoresponsive CB systems have been demonstrated. Although guests such as stilbene analogues 22 , naphthalene/anthracene derivatives 23,24 and coumarins 25 have been used to form 2:1 homoternary complexes with CB [8], their irreversible photodimerizations limit further application in orthogonal switching.…”

“…Recent efforts have been dedicated to gaining orthogonal control over supramolecular systems, whereby different responses can be triggered on demand with a specific order of input stimuli, representing versatility and complexity beyond unifunctional systems 6 . One attractive way to achieve this is to delicately combine host-guest molecular recognition with other non-covalent interactions, for example, metal-ligand or protein-ligand interactions [7][8][9][10] . A major limitation in the field, however, has been the incorporation of multiple responsive components into one single supramolecular entity directly.…”