Phase behavior and dissociation kinetics of lamins in a polymer model of progeria.

This article focuses on modeling the assembly and dynamics of lamin proteins, key structural components of the nuclear lamina, to understand their altered behavior in laminopathic diseases such as Hutchinson–Gilford Progeria Syndrome (HGPS). Using coarse-grained molecular dynamics simulations, lamin supramolecular structures are represented as rod-like polymer chains confined within a spherical shell mimicking the nuclear envelope, allowing investigation of how lamin concentration, lamin–lamin (head–tail) affinity, and lamin–inner nuclear membrane (INM) interactions influence lamina morphology and kinetics. The study reproduces experimentally observed features of HGPS nuclei, including the formation of nematic microdomains, lamina thickening, and suppressed lamin dissociation, demonstrating that these phenotypes arise from an interplay between increased lamin–lamin and lamin–shell affinities at elevated lamin concentrations. While the model simplifies the complex nuclear environment by focusing on a single lamin type and uniform spherical confinement, it provides insights into the physical mechanisms by which mutations affecting lamin interactions contribute to nuclear lamina abnormalities in disease.