The bladder is a highly variable mechanical microenvironment expanding from a few to hundreds of kPa due to functional reasons. Despite that, the urothelial cancer cells become more deformable already at the early stages of cancer progression as measured by atomic force microscopy (AFM).
Over two decades of AFM employment in measurements of elastic and rheological properties of living cells unravel the importance of biomechanics in various aspects of cell functioning. Gathered evidence showed that cell mechanics is not only limited to the mechanical properties of cells. Several structural components contribute to the mechanical properties of bladder cancer cells. Primarily, the organization of polymerized actin form (actin filaments) and the overall actin content are related to cell mechanics. By applying the brush model, the mechanical properties of the cells studied under specific cleavage conditions were correlated with the presence of the particular type of the pericellular glycocalyx layer. The actin cytoskeleton is linked with the focal adhesion molecules; thus, altered expressions of related molecules affect cell deformability. The interactions with multiple components of the extracellular matrix (ECM), particularly basement membranes (BMs, mainly composed of laminins or type IV collagen with large proteoglycan contribution), impact on cancer dissemination. Distinct contributions of cell structural elements to cell biomechanics form a question of the leading cause of cell alterations in mechanical properties during cancer progression. Obtained results reveal not only distinct deformability but also variability in the single-molecule interactions. Our findings show that cell morphological, mechanical, and adhesive properties significantly affect bladder cancer progression.