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

One of the key structural proteins in the eukaryotic cell nucleus is lamin. Lamins can assemble
into a two-dimensional protein meshwork at the nuclear periphery, known as the nuclear lamina,
which provides rigidity and shape to the nucleus. Mutations in lamin proteins that alter the struc-
ture of the nuclear lamina underlie laminopathic diseases, including Hutchinson–Gilford Progeria
Syndrome (HGPS). Experiments have shown that, compared to healthy cells, lamin supramolecular
structures (e.g., protofilaments) assemble into a thicker lamina in HGPS, where they form highly sta-
ble nematic microdomains at the nuclear periphery, reminiscent of liquid crystals. This significantly
alters the morphological and mechanical properties of the nucleus. In this study, we investigate the
aggregation of lamin fibrous structures and their dissociation kinetics from the nuclear periphery
by modeling them as coarse-grained, rod-like polymer chains confined within a rigid spherical shell.
Our model reproduces the formation of multidirectional nematic domains at the nuclear surface and
the reduced lamin dissociation observed in HGPS nuclei by adjusting lamin concentration, lamin-
lamin (head-tail), and lamin-shell association strengths. While nematic phase formation requires
relatively strong lamin-shell affinity under any non-vanishing inter-lamin attraction, the thickness
of the lamina layer is primarily controlled by head-tail association strength in the model. Fur-
thermore, the unbinding kinetics of lamin chains from the lamina exhibit a concentration-dependent
facilitated dissociation, suppressed by strong intra-lamin interactions, reminiscent of diseased nuclei.
Overall, our calculations reveal the physical mechanisms by which mutations affecting native lamin
interactions and concentration could lead to an abnormal nuclear lamina in laminopathic diseases.