Volume regulation of cancer cells during osmotic pressure variation

Abstract Osmotic pressure is a fundamental physical determinant of cellular homeostasis, and its perturbation is recognized as a critical factor in cancer progression and therapy. However, whether cancer cells and normal cells respond to osmotic pressure changes differently remains unclear. Here, we subjected cancer and normal cells to osmotic shocks and compared their volume and traction force changes. Under hypotonic conditions, cancer cells recovered their volume and forces much more slowly than normal cells, although both cell types responded similarly to hypertonic shock. We found that actin-based cortical tension controlled the recovery speed; whereas myosin-mediated contractility tuned the volume change extent. Substrate stiffness also influenced the recovery process by altering cytoskeletal constraint. A theoretical model integrating adhesion energy, ion and water transport, and surface tension was developed. The results matched the experimental observations. Our work uncovered the distinct mechanobiological behaviors of cancer cells upon hypotonic shock, providing a mechanical framework for understanding cancer mechanisms that may inform the development of cancer therapeutics.