Hameed, H. A.; Paturej, J.; Erbas, A.

One of the key structural proteins in the eukaryotic cell nucleus is lamin proteins. Lamins can assemble into a quasi two dimensional protein meshwork at the nuclear periphery, referred to as the nuclear lamina, which provides rigidity and shape to the nucleus. Mutations in lamin proteins that affect the nuclear lamina\'s structure underlie laminopathic diseases, including Hutchinson Gilford Progeria Syndrome (HGPS). Experiments have revealed that, compared to healthy cells, lamin supramolecular structures (e.g., fibers) assemble into a thicker lamina structure in HGPS, where lamins form highly stable nematic microdomains reminiscent of liquid crystals. This significantly alters the morphological and mechanical properties of the nucleus. However, the polymer-physical mechanisms and interactions governing lamin assembly into the nuclear lamina in disease remain relatively poorly understood. In this study, we investigate the aggregation of lamin fibrous structures and their dissociation kinetics by modeling them as rod-like, coarse-grained polymer solutions in a rigid spherical shell. Our model reproduces experimentally observed disease-associated changes in lamin organization by adjusting lamin polymer concentration, lamin-lamin interaction, and lamin-nuclear shell association strength. These changes include the formation of multidirectional nematic domains at the nuclear lamina and slower lamin dissociation observed in HGPS nuclei. Our findings offer molecular-scale insights into the mechanisms of laminopathies, highlighting how an interplay of molecular interactions and lamin concentration influence changes in the lamina\'s properties, such as thickness and kinetics, in HGPS.