The LINC (linker of nucleus to the cytoskeleton) complex spans the perinuclear space, where SUN-domain trimers in the inner nuclear membrane couple to KASH-domain nesprins in the outer nuclear membrane. Through these tethers, cytoskeletal forces reposition and deform the nucleus and influence chromosomal organization. Regions of high nuclear stress have been reported to exhibit locally elevated LINC density, suggesting potential self-association, yet whether and how LINC complexes We combined protein-protein docking with all-atom molecular dynamics simulations to evaluate LINC-LINC interaction topologies. Ten candidate oligomeric arrangements were generated and ranked by complexation free-energy proxies and interface stability. Multiple oligomerization modes are energetically feasible, with head-to-tail linear arrays and branched lattice-like assemblies showing the most favorable interface energetics and longest lifetimes in molecular simulations. We performed energy decomposition of all residues within the binding interface to rank which residue or groups of residues maintain the interaction. Our results support a mechanics-guided assembly model in which LINC oligomerization emerges under load to form stress-bearing superstructures. We propose testable predictions—e.g., mutating key SUN-SUN interface residues or perturbing membrane curvature should modulate clustering—and suggest that disrupting these assemblies could alter chromosomal positioning and nuclear mechanotransduction.
Domkam et al. (Sun,) studied this question.