FIGURE 1.

Step-wise incorporation of lamin isoforms into the nuclear lamina and resulting isoform expression based on cells’ inherent mechanophenotype. (A) B-type lamins enter the nucleus and form the first layer of the nuclear lamina (Step 1). The incorporation of B-type lamins into the nuclear lamina allows them to recruit internalized lamin A isoforms into the nuclear lamina (Step 2). Once lamin A is part of the nuclear lamina, internalized lamin C proteins can attach to the nuclear lamina meshwork (Step 3). All these recruited lamin proteins generate intracellular tension that is relayed into the chromatin network (Step 4), which in part regulates expression of lamins to match the characteristic levels of a given mechanophenotype (Step 5). (B) This intracellular tension-led regulation will upregulate LMNA genes in stiff cells, resulting in cells expressing higher levels of lamin A or C. However, in soft cells, intracellular tension is low, resulting in downregulation of LMNA and upregulation of LMNB1. During these processes, lamin isoforms assemble as homodimers and inter-lamin interactions with the nuclear lamina are facilitated by lamin-binding and other accessory proteins.