Signal Amplification in Highly Ordered Networks Is Driven by Geometry

Vanamee, Eva; Lippner, Gábor; Faustman, Denise L.

doi:10.3390/cells11020272

Cited by 6 publications

(9 citation statements)

References 37 publications

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“…We have shown earlier that cooperative signaling networks can be represented as planar graphs with nodes ( n ) and edges ( e ), where n represents the input signal and e the output signal ( 21 ). Cooperativity requires that at least two n input nodes are placed near each other at the right distance to create an e output.…”

Section: Clustering Enables Cooperativity and Leads To Signal Amplifi...mentioning

confidence: 99%

The benefits of clustering in TNF receptor superfamily signaling

Vanamee,

Faustman

2023

Front. Immunol.

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The tumor necrosis factor (TNF) receptor superfamily is a structurally and functionally related group of cell surface receptors that play crucial roles in various cellular processes, including apoptosis, cell survival, and immune regulation. This review paper synthesizes key findings from recent studies, highlighting the importance of clustering in TNF receptor superfamily signaling. We discuss the underlying molecular mechanisms of signaling, the functional consequences of receptor clustering, and potential therapeutic implications of targeting surface structures of receptor complexes.

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Section: Clustering Enables Cooperativity and Leads To Signal Amplifi...mentioning

confidence: 99%

The benefits of clustering in TNF receptor superfamily signaling

Vanamee,

Faustman

2023

Front. Immunol.

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“…Given the important role of receptor (and other membrane protein) clustering in NP cell interactions, − clearly prescribed reproducible spatial organization and orientation of the receptors at the surface would be more representative of true membrane recognition, but new sensor developments will be required to address those questions. Also, while we can reproducibly control the density of the immobilized receptor during the functionalization of the sensor by following its frequency change, it is more precise to regenerate a single prepared sensor surface between the measurements by inducing the release of bound ligands.…”

Section: Resultsmentioning

confidence: 99%

Quartz Crystal Microbalance Method to Measure Nanoparticle–Receptor Interactions and Evaluate Nanoparticle Design Efficiency

Behan

Xie

Wang

et al. 2023

JACS Au

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Conjugation of biomolecules on the surface of nanoparticles (NPs) to achieve active targeting is widely investigated within the scientific community. However, while a basic framework of the physicochemical processes underpinning bionanoparticle recognition is now emerging, the precise evaluation of the interactions between engineered NPs and biological targets remains underdeveloped. Here, we show how the adaptation of a method currently used to evaluate molecular ligand−receptor interactions by quartz crystal microbalance (QCM) can be used to obtain concrete insights into interactions between different NP architectures and assemblies of receptors. Using a model bionanoparticle grafted with oriented apolipoprotein E (ApoE) fragments, we examine key aspects of bionanoparticle engineering for effective interactions with target receptors. We show that the QCM technique can be used to rapidly measure construct−receptor interactions across biologically relevant exchange times. We contrast random adsorption of the ligand at the surface of the NPs, resulting in no measurable interaction with target receptors, to grafted oriented constructs, which are strongly recognized even at lower graft densities. The effects of other basic parameters impacting the interaction such as ligand graft density, receptor immobilization density, and linker length were also efficiently evaluated with this technique. Dramatic changes in interaction outcomes with subtle alterations in these parameters highlight the general importance of measuring the interactions between engineered NPs and target receptors ex situ early on in the construct development process for the rational design of bionanoparticles.

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“…It’s also detected in detail by nanoscopy that supramolecular cluster of Syntaxin was composed of 75 densely crowded Syntaxins molecules and exhibited diameter of 50 to 60 nanometers ( 36 ). The formation of receptor cluster can boost signaling amplitude by only changing the size and geometric structure of clusters ( 37 ), so Escherichia coli controls the size of the clustering of chemotactic receptors on cell surface to detect and respond to wide range concentration (from less than 5 nM to 5 mM) of aspartate ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

Nav1.7 and Nav1.8 form supramolecular active clusters with TRKB in mouse and human DRG neurons during development of neuropathic pain

Sun

Xian

Shi

et al. 2022

Preprint

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Neuropathic pain affects 7-10% of the global population, and one of its characteristics is sensitization of somatosensory nervous system. Altered expression of ion channels and receptors has been found to be involved in neuronal hyperexcitability after injury to somatosensory nervous system, it is, however, unknown that if ion channels and receptors could gain qualitative changes on the level of structure organization when they are excessively expressed in same one neuron during the development of neuropathic pain. Here we show first that not only the expression of voltage-gated sodium channels Nav1.7 (SCN9A), Nav1.8 (SCN10A) and TRKB (also named NTRK2) increased in DRG neurons of patients with over 3-month severe neuropathic pain induced by brachial plexus avulsion (BPA), but also Nav1.7 and Nav1.8 formed supramolecular active clusters with or without TRKB in DRG neurons of mice with chronic neuropathic pain induced by spared nerve injury or diabetic neuropathy and of BPA pain patients with neuropathic pain. Nav1.7, Nav1.8 and TRKB might function in a coordinated manner in orderly organized supramolecular active clusters to geometrically increase the hyperexcitability of pathological DRG neurons. Our findings suggest that supramolecular active clusters of Nav1.7, Nav1.8 and TRKB might need be targeted for curing neuropathic pain, and that inhibition of both Nav1.7 and Nav1.8 might be required to achieve efficient relief of neuropathic pain.

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Signal Amplification in Highly Ordered Networks Is Driven by Geometry

Cited by 6 publications

References 37 publications

The benefits of clustering in TNF receptor superfamily signaling

The benefits of clustering in TNF receptor superfamily signaling

Quartz Crystal Microbalance Method to Measure Nanoparticle–Receptor Interactions and Evaluate Nanoparticle Design Efficiency

Nav1.7 and Nav1.8 form supramolecular active clusters with TRKB in mouse and human DRG neurons during development of neuropathic pain

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