Glycocalyx Remodeling Shapes Cancer Cell Mechanics

The glycocalyx – a complex meshwork of sugars, proteins, and lipids – coats all human cells and plays a crucial role in cell signaling and immune system regulation. While an understanding of its biochemical functions is emerging, its influence on cell mechanics remains comparably underexplored. Recent evidence suggests that the glycocalyx regulates membrane morphology and cell adhesion, yet its mechanical role has been difficult to study, primarily due to the absence of high-throughput analysis strategies that account for cell-to-cell variability. Here, we overcome this challenge by integrating real-time deformability cytometry (RT-DC) with genetic and chemical glycocalyx engineering to tune the glycocalyx state and assess how cell mechanics are affected. Using this approach, we uncovered mechanical adaptations that contribute to promoting cell migration and metastasis. These findings establish glycocalyx remodeling as a regulator of cancer-cell mechanics and a potential target for therapeutic intervention.