Switching behaviour in vascular smooth muscle cell-matrix adhesion during oscillatory loading

Area of Science:

• Cellular mechanics
• Biophysics
• Biomaterials

Background:

• Integrins mediate mechanotransduction between smooth muscle cells (SMCs) and the extracellular matrix (ECM).
• SMCs in vessels and airways experience dynamic mechanical forces from physiological activities.
• The impact of these forces on integrin dynamics and cell-matrix adhesion remains unclear.

Purpose of the Study:

• To investigate integrin response to external oscillatory loading in live aortic SMCs.
• To understand the effects of varying force amplitudes on cell-matrix adhesion dynamics.
• To develop a mathematical model for simulating integrin-ECM interactions under mechanical stress.

Main Methods:

• Atomic force microscopy (AFM) with a fibronectin-coated probe to apply cyclic indentation to SMCs.
• Observation of adhesion states (firm adhesion vs. detachment) based on force-time courses.
• Development of a mathematical model simulating cell-integrin-ECM as a spring system with local integrin binding dynamics.

Main Results:

• AFM experiments showed a transition from firm adhesion to detachment with increasing oscillatory loading amplitude.
• Switching behavior between adhesion states was observed in some SMCs at intermediate amplitudes.
• The mathematical model reproduced two similar adhesion states and identified a bistability region.
• Bistability in the model, driven by integrin cooperativity and cell deformation, explains experimental switching behavior.

Conclusions:

• Bistability in integrin-mediated adhesion provides a potential mechanism for how transient mechanical stimuli can induce long-term changes in cell-matrix interactions.
• This phenomenon may alter the cells' force transmission capabilities.
• Further experiments are proposed to validate the physiological implications of bistability in SMC adhesion dynamics.