Characterization of poroelastic diffusion in autosomal dominant leukodystrophy cells

The mechanical characteristics of the cell nucleus, often compromised in disease, influence essential processes such as chromatin accessibility. The architecture and structural mechanics of the nucleus are determined by the nuclear lamina, which is composed of A- and B-type lamins. Laminopathies are a group of genetic disorders resulting from mutations in nuclear lamins. Recently, gene duplication and overexpression of lamin B1 (LB1) have been identified in families affected by autosomal dominant leukodystrophy (ADLD), with increased nuclear stiffness observed in correlation with this overexpression [1]. The primary method for characterizing the mechanics of biological materials at the sub-micrometer scale is atomic force microscopy (AFM). This technique allows us to determine the Young's modulus of biomaterials, which could potentially serve as a biomarker for certain pathologies. However, this method requires significant time investment due to the need for a large statistical sample. To address this challenge, we explored an alternative approach using a poroelastic model of the cell combined with the stress-relaxation technique, allowing us to calculate the poroelastic diffusion coefficient (Dp) in living cells [2]. This investigation revealed a significant difference in poroelastic behavior in ADLD cells, which was more pronounced than changes in stiffness alone. This newly identified diagnostic biomarker could offer an innovative approach to studying pathologies related to dysregulated nuclear mechanics. [1] [2] Ferrera, Denise, et al. "Lamin B1 overexpression increases nuclear rigidity in autosomal dominant leukodystrophy fibroblasts." The FASEB Journal 28.9 (2014): 3906. Moeendarbary, Emad, et al. "The cytoplasm of living cells behaves as a poroelastic material." Nature materials 12.3 (2013): 253-261.