Mechanical regulation of cell-cycle progression and division

Cell-cycle progression and division are fundamental biological processes in animal cells, and their biochemical regulation has been extensively studied. An emerging body of work has revealed how mechanical interactions of cells with their microenvironment in tissues, including with the extracellular matrix (ECM) and neighboring cells, also plays a crucial role in regulating cell-cycle progression and division. We review recent work on how cells interpret physical cues and alter their mechanics to promote cell-cycle progression and initiate cell division, and then on how dividing cells generate forces on their surrounding microenvironment to successfully divide. Finally, the article ends by discussing how force generation during division potentially contributes to larger tissue-scale processes involved in development and homeostasis. Tissue-level tension, cytoskeletal tension, and stiff substrates for 2D culture generally promote cell-cycle progression and division, whereas confining environments or compression inhibit cell growth, leading to delayed or halted cell-cycle progression and division.Cells dividing in confining environments generate extracellular forces to drive major morphological changes which are necessary for proper division completion, including mitotic rounding, division elongation, and postdivision spreading.Extracellular forces generated during cell division contribute to cell migration and tissue-scale processes important in development, including tissue growth, invagination, luminogenesis, and epithelial stratification.Cancer cells are able to undergo cell-cycle progression and cell division within the confining tumor microenvironment.