A team of researchers led by VCU College of Engineering and the University of Florida has found a possible mechanical explanation for how cell structure and tissue can be disrupted, which may provide clues into what happens in diseases such as cancer.
Daniel Conway, Ph.D., associate professor in the Department of Biomedical Engineering, is investigating the role of mechanical forces on cells and what makes normal cells stable. Epithelial cells, which separate the body from the outside environment and provide barriers between different areas inside organs such as the liver, are critical for tissue and organ function. Problems with these cells are linked to defective wound healing and the development and progression of cancer.
Conway is a co-author of a study that identified the importance of a group of proteins known as the nuclear linker of nucleoskeleton to cytoskeleton (LINC) complex, which anchors the nucleus to the cellular cytoskeleton. The study using 3D culture models of acini, or cysts or spheroids, suggests that mechanically disrupting the LINC complex destabilizes the acini. The article will be published in the September issue of Current Biology.
“We are interested in how the nucleus inside the cell is mechanically integrated into the cellular cytoskeleton,” Conway said. “If you disrupt the structure mechanically, the cells — and by extension, the tissue — are disturbed.”
Vani Narayanan, doctoral candidate in the Department of Biomedical Engineering and lead co-author of the study, said, “If these main connections that help anchor the nucleus are disrupted, the cells try their best to compensate in order to keep things normal. Unfortunately, this compensation becomes over-compensation. 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.”
Conway said they are seeking to understand how multicellular structures organize and form and what makes them remain stable. “What are the fundamental mechanical properties of the cell that are required to make and stabilize this structure?”