Surface topography modulates cancer cell function and mechanical adaptation

The physical microenvironment regulates cancer cell behavior through mechanical and geometrical cues. While surface topography is known to influence cell adhesion and proliferation, its effects on population-level behaviors and time-dependent adaptation remain unclear. Here, we developed a simple particle-coating method to generate isotropic topographies (0.7 μm and 2.26 μm) directly in standard culture wells and applied it to melanoma cell lines. Topography did not affect viability but induced a more contractile morphology, reduced migration, and increased proliferation, with stronger effects for 2.26 μm particles. Topography also induced a biphasic proliferative response, with an initial increase followed by a later decline after serial passaging. Transcriptomic analysis revealed upregulation of metabolic and adhesion pathways, supporting early increases in proliferation and adhesion while prolonged activation may cause metabolic stress and reduced proliferation. Overall, these topographies modulate melanoma behavior via adhesion and metabolism changes, offering a simple platform to study time-dependent cellular responses. • Cost-effective method to engineer colloidal topographic cell-culture surfaces. • Defined surface cues alter cancer cell proliferation and migration. • Topography induces long-term adaptive cancer cell states. • Enables routine integration of mechanical context in vitro. • Supports discovery of mechanically driven metabolic vulnerabilities.