Multivalent Affinity Profiling: Direct Visualization of the Superselective Binding of Influenza Viruses

Overeem, Nico J.; Hamming, P. H. Erik; Tieke, Malte; Vries, Erhard van der; Huskens, Jurriaan

doi:10.1021/acsnano.1c00166

Cited by 16 publications

(31 citation statements)

References 53 publications

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Section: Results and Discussionmentioning

confidence: 99%

“…The results show that the NP tends to establish a higher number of multivalent interactions with the surface groups while moving toward denser surface regions, as recently demonstrated with fluorescent microscopy experiments in other multivalent binding systems. 19 Such enhancement of the multivalent binding with the surface leads to an increased exposure of the hydrophobic parts of the NP oligomers to the solvent, thereby entailing an increase of the SASA of the assembly (ΔSASA). The ΔSASA increases even further as a consequence of NP exfoliation, as well illustrated in Figure 5b.…”

Section: Resultsmentioning

confidence: 99%

“…The identification of a threshold receptor density as a function of multivalent interactions has been recently estimated by a sophisticated image postprocessing approach. 19 However, perhaps the main advantage of these self-assembling oligomers is that their modular structure enables the finetuning of hydrophobic/hydrophilic groups in order to control the NP disassembly and the release of the guests during the NP chemotaxis. While the ΔE ass /ΔE bind ratio is critical to control the chemotactic responsive behavior of the NPs, our simulations highlight how such a control can be achieved by for example, modulating the multivalent interactions between the NP and the surface, or even by changing the number of −1e charged groups on the oligomers (namely, changing the ΔE ass /ΔE bind by acting on the ΔE bind ).…”

Section: Resultsmentioning

confidence: 99%

“…Notable examples of synthetic supramolecular structures, such as fibers, vesicles, or tubes have demonstrated to have excellent stimuli responsive properties while autonomously moving. − Also responsive nanoparticles (NPs) have shown surface binding capability combined with tailored releasing of encapsulated guests. − To predict and engineer the selective binding on surfaces, both monovalent and multivalent affinities are exploited. To cite just a few examples, Liao et al studied the correlation between monovalent labeling schemes on a gold NP and its diffusion rate on supported lipid bilayer membranes, while Overseem and co-workers investigated multivalent binding profiles of influenza virus on surfaces with receptor density gradients . However, despite notable advances in surface modification and control are emerging thanks to cutting-edge techniques, technical experimental limitations still prevent the rational design of chemotactic functional materials.…”

mentioning

confidence: 99%

“…To cite just a few examples, Liao et al studied the correlation between monovalent labeling schemes on a gold NP and its diffusion rate on supported lipid bilayer membranes, 18 while Overseem and co-workers investigated multivalent binding profiles of influenza virus on surfaces with receptor density gradients. 19 However, despite notable advances in surface modification and control are emerging thanks to cutting-edge techniques, 20 technical experimental limitations still prevent the rational design of chemotactic functional materials. First, tracking and observing the movement of soft, tiny NPs on surfaces at sufficiently small spatiotemporal scales is a hard challenge.…”

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confidence: 99%

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Toward Chemotactic Supramolecular Nanoparticles: From Autonomous Surface Motion Following Specific Chemical Gradients to Multivalency-Controlled Disassembly

et al. 2021

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Nature designs chemotactic supramolecular structures that can selectively bind specific groups present on surfaces, autonomously scan them moving along density gradients, and react once a critical concentration is encountered. Since such properties are key in many biological functions, these also offer inspirations for designing artificial systems capable of similar bioinspired autonomous behaviors. One approach is to use soft molecular units that self-assemble in an aqueous solution generating nanoparticles (NPs) that display specific chemical groups on their surface, enabling multivalent interactions with complementarily functionalized surfaces. However, a first challenge is to explore the behavior of these assemblies at sufficiently high-resolution to gain insights on the molecular factors controlling their behaviors. Here, by coupling coarse-grained molecular models and advanced simulation approaches, we show that it is possible to study the (autonomous or driven) motion of self-assembled NPs on a receptor-grafted surface at submolecular resolution. As an example, we focus on self-assembled NPs composed of facially amphiphilic oligomers. We observe how tuning the multivalent interactions between the NP and the surface allows to control of the NP binding, its diffusion along chemical surface gradients, and ultimately, the NP reactivity at determined surface group densities. In silico experiments provide physical–chemical insights on key molecular features in the self-assembling units which determine the dynamic behavior and fate of the NPs on the surface: from adhesion, to diffusion, and disassembly. This offers a privileged point of view into the chemotactic properties of supramolecular assemblies, improving our knowledge on how to design new types of materials with bioinspired autonomous behaviors.

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Section: Results and Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Toward Chemotactic Supramolecular Nanoparticles: From Autonomous Surface Motion Following Specific Chemical Gradients to Multivalency-Controlled Disassembly

et al. 2021

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Determinants of Superselectivity─Practical Concepts for Application in Biology and Medicine

2023

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Conspectus Multivalent interactions are common in biological systems and are also widely deployed for targeting applications in biomedicine. A unique feature of multivalent binding is “superselectivity”. Superselectivity refers to the sharp discrimination of surfaces (e.g., on cells or cell compartments) by their comparative surface densities of a given receptor. This feature is different from the conventional “type” selectivity, which discriminates surfaces by their distinct receptor types. In a broader definition, a probe is superselective if it converts a gradual change in any one interaction parameter into a sharp on/off dependency in probe binding. This Account describes our systematic experimental and theoretical efforts over the past decade to analyze the determinants of superselective binding. It aims to offer chemical biologists, biophysicists, biologists, and biomedical scientists a set of guidelines for the interpretation of multivalent binding data, and design rules for tuning superselective targeting. We first provide a basic introduction that identifies multiple low-affinity interactions and combinatorial entropy as the minimal set of conditions required for superselective recognition. We then introduce the main experimental and theoretical tools and analyze how salient features of the multivalent probes (i.e., their concentration, size, ligand valency, and scaffold type), of the surface receptors (i.e., their affinity for ligands, surface density, and mobility), and of competitors and cofactors (i.e., their concentration and affinity for the ligands and/or receptors) influence the sharpness and the position of the threshold for superselective recognition. Emerging from this work are a set of relatively simple yet quantitative data analysis guidelines and superselectivity design rules that apply to a broad range of probe types and interaction systems. The key finding is the scaling variable x S which faithfully predicts the influence of the surface receptor density, probe ligand valency, receptor–ligand affinity, and competitor/cofactor concentrations and affinities on superselective recognition. The scaling variable is a simple yet versatile tool to quantitatively tune the on/off threshold of superselective probes. We exemplify its application by reviewing and reinterpreting literature data for selected biological and biomedical interaction systems where superselectivity clearly is important. Our guidelines can be deployed to generate a new mechanistic understanding of multivalent recognition events inside and outside cells and the downstream physiological/pathological implications. Moreover, the design rules can be harnessed to develop novel superselective probes for analytical purposes in the life sciences and for diagnostic/therapeutic intervention in biomedicine.

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Designing Multivalent Copolymers for Selective Targeting of Multicomponent Surfaces

Ravnik,

Bren,

Curk

2024

Macromolecules

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Selective targeting of membranes with a specific receptor profile is an ongoing challenge in targeted drug delivery. We investigate the adsorption of copolymers on a multicomponent receptor-covered surface using grand-canonical Monte Carlo simulations and demonstrate that polymers can be designed to target a particular receptor density profile. To achieve this, the ligand profile on the polymers should match the targeted receptor profile, and the ligand−receptor affinity should be inversely proportional to the ligand profile. While the same can be obtained using multivalent nanoparticles, the entropic effects due to polymer conformations significantly enhance the binding selectivity of multivalent polymers compared to nanoparticles. Surprisingly, the ligand distribution on the polymer plays a crucial role, whereas the persistence length does not. The optimal selectivity to the overall receptor concentration is obtained by the Poisson distribution of ligands (random copolymer), whereas the maximal selectivity to a specific receptor profile is obtained by a defined sequence of grouped alternating ligands (regular copolymer). Interestingly, the regular copolymer can become anti-selective when ligands of the same type are in homogeneous blocks, showing that specific ligand distribution qualitatively affects the targeting ability. These findings suggest that sequence control is necessary to selectively target a specific density profile of membrane receptors using linear copolymers.

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Multivalent Affinity Profiling: Direct Visualization of the Superselective Binding of Influenza Viruses

Cited by 16 publications

References 53 publications

Toward Chemotactic Supramolecular Nanoparticles: From Autonomous Surface Motion Following Specific Chemical Gradients to Multivalency-Controlled Disassembly

Toward Chemotactic Supramolecular Nanoparticles: From Autonomous Surface Motion Following Specific Chemical Gradients to Multivalency-Controlled Disassembly

Determinants of Superselectivity─Practical Concepts for Application in Biology and Medicine

Designing Multivalent Copolymers for Selective Targeting of Multicomponent Surfaces

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