ArticleBiophysical journal2013
Pleomorphic ensembles: formation of large clusters composed of weakly interacting multivalent molecules.
Article in Biophysical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Semisynthetic Ferritin Nanocages for Flexible, Site-Specific Targeting and Ligand-Free Activation of Membrane Receptors.Nano letters · 2025Article
- Protein interactions, calcium, phosphorylation, and cholesterol modulate CFTR cluster formation on membranes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Measurement of solubility product reveals the interplay of oligomerization and self-association for defining condensate formation.Molecular biology of the cell · 2024Article
- Modular RNA motifs for orthogonal phase separated compartments.Nature communications · 2024Article
- Multi-condensate state as a functional strategy to optimize the cell signaling output.Nature communications · 2024Article
- Multi-condensate state as a functional strategy to optimize the cell signaling output.bioRxiv : the preprint server for biology · 2024Article
- Measurement of solubility product in a model condensate reveals the interplay of small oligomerization and self-association.bioRxiv : the preprint server for biology · 2024Article
- MolClustPy: a Python package to characterize multivalent biomolecular clusters.Bioinformatics (Oxford, England) · 2023Article
- The maximum solubility product marks the threshold for condensation of multivalent biomolecules.Biophysical journal · 2023Article
- MolClustPy: A Python Package to Characterize Multivalent Biomolecular Clusters.bioRxiv : the preprint server for biology · 2023Article
- Different states and the associated fates of biomolecular condensates.Essays in biochemistry · 2022Review
- Nanoscale regulation of CaNature communications · 2022Article
- Surface tension and super-stoichiometric surface enrichment in two-component biomolecular condensates.iScience · 2022Article
- The solubility product extends the buffering concept to heterotypic biomolecular condensates.eLife · 2021Article
- A Hypothesis: Linking Phase Separation to Meiotic Sex Chromosome Inactivation and Sex-Body Formation.Frontiers in cell and developmental biology · 2021Review
- Designer protein assemblies with tunable phase diagrams in living cells.Nature chemical biology · 2020Article
- The bioenergetics of integrin-based adhesion, from single molecule dynamics to stability of macromolecular complexes.Computational and structural biotechnology journal · 2020Review
- A predictive computational model reveals that GIV/girdin serves as a tunable valve for EGFR-stimulated cyclic AMP signals.Molecular biology of the cell · 2019Article
- The Interplay of Structural and Cellular Biophysics Controls Clustering of Multivalent Molecules.Biophysical journal · 2019Article
- An Overview of Network-Based and -Free Approaches for Stochastic Simulation of Biochemical Systems.Computation (Basel, Switzerland) · 2018Article
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3 authors.
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Abstract
Molecular interactions of importance to cell biology are subject to sol-gel transitions: large clusters of weakly interacting multivalent molecules (gel phase) are produced at a critical concentration of monomers. Examples include cell-cell and cell-matrix adhesions, nucleoprotein bodies, and cell signaling platforms. We use the term pleomorphic ensembles (PEs) to describe these clusters, because they have dynamic compositions and sizes and have rapid turnover of their molecular constituents; this plasticity can be highly responsive to cellular signals. The classical polymer physical chemistry theory developed by Flory and Stockmayer provides a brilliant framework for treating multivalent interactions for simple idealized systems. But the complexity and variability of PEs challenges existing modeling approaches. Here we describe and validate a computational algorithm that extends the Flory-Stockmayer formalism to overcome the limitations of analytic theories. We divide the problem by deterministically calculating the fraction of bound sites for each type of binding site, followed by the stochastic assignment of the bonds to a finite number of molecules. The method allows for high valency within many different kinds of interacting molecules and site types, permits simulation of steady-state distributions, as well as assembly kinetics, and can treat cooperative binding within one of the interacting molecules. We then apply our method to the analysis of interactions in the nephrin-Nck-N-Wasp signaling system, demonstrating how multivalent layered scaffolds produce PEs at low monomer concentrations despite weak binding interactions. We show how the experimental data for this system are most consistent with synergistic cooperative interactions between Nck and N-Wasp.
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