Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Elastic versus Brittle Mechanical Responses Predicted for Dimeric Cadherin Complexes Cadherins are a superfamily of adhesion proteins involved in a variety of biological processes that include the formation of intercellular contacts, the maintenance of tissue integrity, and the development of neuronal circuits. These transmembrane proteins are characterized by ectodomains composed of a variable number of extracellular cadherin (EC) repeats that are similar but not identical in sequence and fold. E-cadherin, along with desmoglein and desmocollin proteins, are three classical-type cadherins that have slightly curved ectodomains and engage in homophilic and heterophilic interactions through an exchange of conserved tryptophan residues in their N-terminal EC1 repeat. In contrast, clustered protocadherins are straighter than classical cadherins and interact through an antiparallel homophilic binding interface that involves overlapped EC1 to EC4 repeats. Here we present molecular dynamics simulations that model the adhesive domains of these cadherins using available crystal structures, with systems encompassing up to 2.8 million atoms. Simulations of complete classical cadherin ectodomain dimers predict a two-phased elastic response to force in which these complexes first softly unbend and then stiffen to unbind without unfolding. Simulated , {beta}, and {gamma} clustered protocadherin homodimers lack a two-phased elastic response, are brittle and stiffer than classical cadherins, and exhibit complex unbinding pathways that in some cases involve transient intermediates. We propose that these distinct mechanical responses are important for function, with classical cadherin ectodomains acting as molecular shock absorbers and with stiffer clustered protocadherin ectodomains facilitating overlap that favors binding specificity over mechanical resilience. Overall, our simulations provide insights into the molecular mechanics of single cadherin dimers relevant in the formation of cellular junctions essential for tissue function.

Statement of SignificanceMulticellular organisms rely on cellular adhesion to survive, and this adhesion is mediated by diverse sets of proteins that include cadherins responsible for organ assembly and tissue integrity maintenance. As parts of cell-cell junctions in epithelial and cardiac tissues, classical cadherins experience forces and must be mechanically robust. In contrast, clustered protocadherins are responsible for neuronal connectivity and are exposed to more subtle mechanical stimuli. We used simulations to study the mechanics of isolated cadherin complexes and found that classical cadherins exhibit a two-phased elastic response that might prevent loss of adhesion during mild mechanical stress. Conversely, we predict that clustered protocadherin complexes are brittle. Our results suggest that each set of cadherins has evolved to adopt distinct mechanical properties.
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The categories of this paper are: animal
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The categories of this paper are: toxicology
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The categories of this paper are: pharmacology
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The categories of this paper are: evolutionary
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The categories of this paper are: pathology
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The categories of this paper are: genomics
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The categories of this paper are: plant
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The categories of this paper are: and
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The categories of this paper are: developmental
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The categories of this paper are: physiology
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The categories of this paper are: microbiology
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The categories of this paper are: molecular
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The categories of this paper are: scientific
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The categories of this paper are: neuroscience
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The categories of this paper are: bioinformatics
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The categories of this paper are: cancer