Viscoelastic Mechanical Models of the LINC Complex

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Cell adhesion, cell spreading and cell-cell communications depend on mechanotransduction processes. Mechanical signals are sensed by integrins on the plasma membrane and then cross the cytoplasm through mechantransduction pathways ultimately reaching chromosomes, eliciting changes in gene expressions. One of the critical parts of these mechanochemical pathways is the linker of the nucleoskeleton and cytoskeleton, known as the LINC complexes. LINC complexes comprise two main proteins, SUN and KASH (a peptide at the tip of Nesprins). The stable connection between SUN and KASH is necessary for cell functioning. In this study, we modeled LINC complex with the combination of different viscoelastic compartments based closely on our molecular dynamic simulations. We divided the LINC complex to different sections connected by spring-dashpot viscoelastic models. We use these viscoelastic models to incorporate and interrogate the contribution of different components of the LINC complex. For example, we investigated the threshholding effect of disulfide bond between C6862 residue of KASH2 and C536 of SUN2 domain on the force transmission, which, as we previously showed, plays a critical role in LINC complex function. Here, we tuned model parameters to model truncated KASH and cysteine-mutated LINC based on our previous molecular dynamic simulations. Our proposed viscoelastic model allows us to investigate the effect of different factors such as proposed mutations on the signal transmission through LINC with tuning model parameters. Together with our all-atom molecular dynamics models, these viscoelastic models can help us gain a better understanding of the LINC complex in the context of other mechanochemical elements of mechanotransduction pathway.