Synergistic Effects of Matrix Biophysical Properties on Gastric Cancer Cell Behavior via Integrin‐Mediated Cell‐ECM Interactions

Abstract The biophysical properties of the extracellular matrix (ECM) play a pivotal role in modulating cancer progression via cell‐ECM interactions. However, the biophysical properties specific to gastric cancer (GC) remain largely unexplored. Pertinently, GC ECM shows significantly heterogeneous metamorphoses, such as matrix stiffening and intricate restructuring. By combining collagen I and alginate, this study designs an in vitro biomimetic hydrogel platform to independently modulate matrix stiffness and structure across a physiological stiffness spectrum while preserving consistent collagen concentration and fiber topography. With this platform, this study assesses the impacts of matrix biophysical properties on cell proliferation, migration, invasion, and other pivotal dynamics of AGS. The findings spotlight a compelling interplay between matrix stiffness and structure, influencing both cellular responses and ECM remodeling. Furthermore, this investigation into the integrin/actin‐collagen interplay reinforces the central role of integrins in mediating cell‐ECM interactions, reciprocally sculpting cell conduct, and ECM adaptation. Collectively, this study reveals a previously unidentified role of ECM biophysical properties in GC malignant potential and provides insight into the bidirectional mechanical cell‐ECM interactions, which may facilitate the development of novel therapeutic horizons.