The Paradox of Nuclear Lamins in Pathologies: Apparently Controversial Roles Explained by Tissue-Specific Mechanobiology

Abstract

The nuclear lamina is a complex meshwork of intermediate filaments (lamins) that is located beneath the inner nuclear membrane and the surrounding nucleoplasm. The lamins exert both structural and functional roles in the nucleus and, by interacting with several nuclear proteins, are involved in a wide range of nuclear and cellular activities. Due their pivotal roles in basic cellular processes, lamin gene mutations, or modulations in lamin expression, are often associated with pathological conditions, ranging from rare genetic diseases, such as laminopathies, to cancer. Although a substantial amount of literature describes the effects that are mediated by the deregulation of nuclear lamins, some apparently controversial results have been reported, which may appear to conflict with each other. In this context, we herein provide our explanation of such "controversy", which, in our opinion, derives from the tissue-specific expression of nuclear lamins and their close correlation with mechanotransduction processes, which could be very different, or even opposite, depending on the specific mechanical conditions that should not be compared (a tissue vs. another tissue, in vivo studies vs. cell cultures on glass/plastic supports, etc.). Moreover, we have stressed the relevance of considering and reproducing the "mechano-environment" in in vitro experimentation. Indeed, when primary cells that are collected from patients or donors are maintained in a culture, the mechanical signals deriving from canonical experimental procedures of cell culturing could alter the lamin expression, thereby profoundly modifying the assessed cell type, in some cases even too much, compared to the cell of origin.

Keywords: cancer; in vitro experimentation; lamins; stiffness; tissue mechanobiology.