Molecular force gates regulate mechanical transmission across the nuclear envelope
Year: 2026
Type: article
Abstract: The LINC (linker of nucleoskeleton and cytoskeleton) complex is a central mechanotransductive apparatus that physically couples cytoskeletal forces to the nuclear interior, thereby regulating nuclear architecture, chromatin organization, and downstream signaling. Using atomistic molecular dynamics simulations, we identify and characterize ‘force gates’ within the LINC complex – structural interactions that maintain mechanical connectivity under load. By introducing targeted mutations into the KASH peptide and SUN protein, we provide computational evidence that a key disulfide bond (SUN2 Cys563–KASH2 Cys6862) and specific residues within the KASH β-strand interaction motif (KASH6875, KASH6877) act as distinct mechanical elements during force transmission across the SUN–KASH interface. By resolving how distinct molecular contacts contribute to force transmission in space and sequence, this work provides experimentally testable predictions for how individual interface interactions govern nuclear force transmission. More broadly, the force-gate framework offers a basis for studying force-bearing interfaces in other mechanically regulated proteins
Source: Figshare
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7225647386
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