Apart from storing most of the DNA in eukaryotic cells, the cell nucleus provides mechanical protection through its nuclear envelope to ensure the integrity of the genome. The nuclear lamina is known to play an important role in this respect by supplying a structural framework for the nucleus [1]. The severe diseases arising from mutations in the LMNA gene confirm the importance of the lamin proteins for normal cell functionality [2]. Most experimental techniques for investigation of the cell mechanics are based on the application of external forces onto the cell boundary [3]. Thus, the quantitative determination of the mechanical properties of intracellular structures in situ, still represents a challenging task. In our previous works, we proposed a 3D image- and model-based framework for analysis of intracellular mechanics [4]. In this work, we extend this approach to a fully contactless investigation of nuclear mechanics of normal and LMNA–/– mutant cells. Differently from previous approaches, cellular deformation was induced by chemical agents, i.e., without any mechanical contact with the cell boundary. In particular, we focus on (i) comparative analysis of 3D structural response of nuclear matter with respect to external forces in normal and pathological cell, as well as (ii) determination of the scarcely-investigated nuclear compressibility (i.e. the Poisson’s ratio).

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