Multicellular Aligned Bands Disrupt Global Collective Cell Behavior

This study investigates how local cell–cell interactions disrupt global collective behavior in micropatterned multicellular aggregates of valvular interstitial cells. Despite symmetric geometric constraints, VICs formed highly aligned multicellular bands that generated heterogeneous traction stresses, altered proliferation, and increased apoptosis in hyperconfluent regions. Cyclic uniaxial stretch revealed that cells within these bands respond differently to mechanical loading depending on orientation, highlighting the role of emergent local mechanics in valve tissue remodeling and disease progression.