Scaling laws indicate distinct nucleation mechanisms of holes in the nuclear lamina

During a first-order phase transition, an interfacial layer is formed between the coexisting phases and kinetically limits homogeneous nucleation of the new phase in the original phase. This inhibition is commonly alleviated by the presence of impurities, often of unknown origin, that serve as heterogeneous nucleation sites for the transition. Living systems present a theoretical opportunity: the regulated structure of living systems allows modelling of the impurities, enabling quantitative analysis and comparison between homogeneous and heterogeneous nucleation mechanisms, usually a difficult task. Here, we formulate an analytical model of heterogeneous nucleation of holes in the nuclear lamina, a phenomenon with implications in cancer metastasis, ageing and other diseases. We then present measurements of hole nucleation in the lamina of nuclei migrating through controlled constrictions and fit the experimental data to our heterogeneous nucleation model as well as a homogeneous model. Surprisingly, we find that different mechanisms dominate depending on the density of filaments that comprise the nuclear lamina