Model for how retrograde actin flow regulates adhesion traction stresses

Cells interact with their environment through adhesion mechanisms that involve mechanical forces. These forces are essential for processes like migration and tissue organization. However, the coordination of intracellular molecules to regulate adhesion remains unclear. While it is known that actin cytoskeleton flows from the cell periphery toward the center, the relationship between this flow and traction forces is not fully understood. Existing studies have shown that integrins and actin linkages are involved in force transmission. Yet, how these components dynamically respond to flow is still debated. Theoretical models are needed to explain how flow affects adhesion stability. This gap motivates the need for a framework that links flow speed to traction stress. The current work aims to address this by exploring how retrograde actin flow influences adhesion forces.

The study aims to investigate how retrograde actin flow influences adhesion traction stresses in cells. It focuses on the relationship between flow speed and the forces generated at the cell-substrate interface. The goal is to develop a theoretical model that explains how molecular complexes respond to flow. This model could clarify how cells regulate adhesion forces during movement. The researchers propose that molecular stretching and breaking due to flow contribute to traction dynamics. By simulating these interactions, they seek to identify the mechanisms that govern adhesion stability. The study also aims to compare slip and catch bond behaviors in integrins. Ultimately, the model should provide insights into how cells control adhesion forces through cytoskeletal dynamics.

The researchers developed a theoretical framework to model adhesion traction stresses. They considered molecular complexes that stretch under drag from retrograde actin flow. The model assumes that these complexes break with extension-dependent kinetics. The team simulated how flow speed affects the number of intact complexes. They analyzed how the competition between stretching and breaking influences traction forces. The model incorporates clutch-like behavior, where forces increase and then decrease with flow speed. The researchers tested slip and catch bond mechanisms for integrins. They extended the model to include multiple molecular interfaces to study stress distribution.

The model shows that traction stresses depend on retrograde actin flow speed in a nonmonotonic way. At low flow speeds, stresses increase due to molecular stretching. However, at higher speeds, the number of intact complexes decreases, leading to reduced stresses. The researchers found that catch bond mechanisms better fit experimental data than slip bonds. Integrins that strengthen under force provide better adhesion stability. When multiple molecular interfaces are included, peak stress shifts to higher flow speeds. The model explains how adhesion forces can be regulated dynamically. The results align with observations in epithelial cells, where traction forces vary with flow. The framework provides a basis for understanding how cells modulate adhesion through cytoskeletal dynamics.

The model demonstrates that retrograde actin flow influences adhesion traction stresses through molecular stretching and breaking. The nonmonotonic trend in stresses suggests a clutch-like mechanism for adhesion regulation. Catch bond behavior in integrins improves the model's fit with experimental data. Multiple molecular interfaces shift the peak stress to higher flow speeds. These findings support the idea that cells use dynamic molecular interactions to control adhesion forces. The model provides a theoretical basis for further studies on adhesion mechanics. It also highlights the importance of flow speed in determining adhesion stability. The results suggest that integrin behavior and cytoskeletal flow are tightly linked in cellular processes.