According to the research study, researchers identifying the fundamental properties of the cells; that affect how tissue structures form. These finding that changing the mechanical properties of individual cells disrupts their ability to remain stable; and profoundly affecting their health and the health of the tissue that comprises them.
The LINC complex a group of proteins knowing as the nuclear linker of nucleoskeleton to the cytoskeleton anchors the nucleus to the cell. The study, using 3-D culture models of cell clusters known as acini; suggesting that mechanically disrupting the LINC complex destabilizes the clusters. If these main connections that help anchor the nucleus are disrupted, the cells try their best to compensate in order to keep things normal.
Various proteins that should ideally remain in nominal amounts within the cell for proper cellular function get unregulated, causing rapid movement of cells within the acinus, abnormal cell division and migration and, hence, the system collapses. Problems with cells such as epithelial cells which separate the body from the outside environment and provide barriers between different areas inside organs; such as the liver, and are critical for tissue and organ function are linking to the defective wound healing; and the development and progression of diseases such as cancer.
Properties of the cells
As the nucleoskeleton and cytoskeleton are important protein networks that govern cellular behavior and are connected together by the linker of nucleoskeleton and cytoskeleton (LINC) complex. Mutations in LINC complex components may be relevant to cancer; but how cell-level changes might translate into tissue-level malignancy is unclear.
The study showing that inducible LINC complex disruption in human mammary epithelial; MCF-10A cells and canine kidney epithelial MDCK II cells mechanically destabilizes the acinus. Lumenal collapse occuring because the acinus is unstable to increasing mechanical tension that is causing by upregulation of Rho kinase dependent non-muscle myosin II motor activity.
Tissue level malignancy
Specifically, a convincing explanation for how cell level; changes translate into tissue level malignancy is lacking, in part because of the limited insight provided by the two-dimensional cell culture used in most studies. Using glandular epithelial cells in a three-dimensional culture model to investigate; the effect of LINC disruption on higher order cellular architecture.
These results, together with our observations; suggest that lumenal filling will occur upon increase in actomyosin tension, independent of the type of perturbations. Our dynamic imaging experiments of the process of lumenal collapse suggest that; increased cellular actomyosin tension due to treatment with calyculin A or Rho activator II or due to LINC complex disruption; caused lumenal collapse through an inward movement of thickening acinar boundaries toward thinning acinar surfaces.