Cell aggregates’ wetting of tumor invasion illustrated by bionic TACS-3 microstructures

Abstract The extracellular matrix collagen fibers at tumor invasion fronts can reorganize into tumor-associated collagen signature-3 (TACS-3), forming hallmark topologies in guiding metastatic migration. It remains unclear how the TACS‑3‑like architecture regulates the collective invasion and wetting dynamics of tumor cell aggregates. Here, we propose a pathology-feature-driven strategy to develop bionic TACS-3 microstructures incorporating Livistona chinensis (LC) and the parallel line (P) structures for the systematic investigation of tumor wetting mechanisms. Large-area, high-fidelity microstructures were efficiently fabricated by the femtosecond laser maskless projection lithography. Experimental results reveal that LC structures promote rapid multidirectional radial wetting, whereas P structures impose constrained uniaxial rail-type wetting. Soft-matter wetting theory further indicates that geometric guidance modulates collective wetting by adhesion energy and the effective spreading coefficient. Quantitative and cellular analyses verify the distinct behaviors induced by differential cytoskeletal polarization and vinculin activation. This study would establish a novel bionic protocol for elucidating topology-guided tumor invasion.