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• W1983602959 abstract "Catch-bonds refer to the counterintuitive notion that the average lifetime of a bond has a maximum at a nonzero applied force. They have been found in several ligand-receptor pairs and their origin is still a topic of debate. Here, we use coarse-grained simulations and kinetic theory to demonstrate that a multimeric protein, with self-interacting domain pairs, can display catch-bond behavior. Our model is motivated by one of the largest proteins in the human body, the von Willebrand Factor, which has been found to display this behavior. In particular, our model polymer consists of a series of repeating units that self-interact with their nearest neighbors along the chain. Each of the units mimics a domain of the protein. Apart from the short-range specific interaction, we also include a linker chain that will hold the domains together if unbinding occurs. This linker molecule represents the sequence of unfolded amino acids that connect contiguous domains, as is typically found in multidomain proteins. The units also interact with an immobilized ligand, but the interaction is masked by the presence of the self-interacting neighbor along the chain. Our results show that this model displays all the features of catch-bonds because the average lifetime of a binding event between the polymer and the immobilized receptor has a maximum at a nonzero pulling force of the polymer. The effects of the energy barriers for detaching the masking domain and the ligand from the binding domain, as well as the effects of the properties of the polypeptide chain connecting the contiguous domains, are also studied. Our study suggests that multimeric proteins can engage in catch-bonds if their self-interactions are carefully tuned, and this mechanism presumably plays a major role in the mechanics of extracellular proteins that share a multidomain character. Furthermore, our biomimetic design clearly shows how one could build and tune macromolecules that exhibit catch-bond characteristics." @default.
• W1983602959 created "2016-06-24" @default.
• W1983602959 creator A5006707355 @default.
• W1983602959 creator A5086120790 @default.
• W1983602959 date "2011-01-01" @default.
• W1983602959 modified "2023-09-26" @default.
• W1983602959 title "Polymer-Based Catch-Bonds" @default.
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• W1983602959 doi "https://doi.org/10.1016/j.bpj.2010.11.023" @default.
• W1983602959 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3010015" @default.
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• W1983602959 hasPublicationYear "2011" @default.
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