Abstract
AIMS: The regulation of vascular diameter by vasoconstrictors and vasodilators requires that vascular smooth muscle cells (VSMCs) be physically coupled to extracellular matrix (ECM) and neighbouring cells in order for a vessel to mechanically function and transfer force. The hypothesis was tested that integrin-mediated adhesion to the ECM is dynamically up-regulated in VSMCs during contractile activation in response to a vasoconstrictor and likewise down-regulated during relaxation in response to a vasodilator. METHODS AND RESULTS: VSMCs were isolated from the Sprague-Dawley rat cremaster muscles. Atomic force microscopy (AFM) with fibronectin (FN)-functionalized probes was employed to investigate the biomechanical responses and adhesion of VSMCs. Responses to angiotensin II (Ang II; 10(-6) M) and adenosine (Ado; 10(-4) M) were recorded by measurements of cell cortical elasticity and cell adhesion. The results showed that Ang II caused an immediate increase in adhesion (+27%) between the probe and cell. Cell stiffness increased (+70%) in parallel with the adhesion change. Ado decreased adhesion (-15%) to FN and reduced (-30%) stiffness. CONCLUSION: Changes in the receptor-mediated activation of the contractile apparatus cause parallel alterations in cell adhesion and cell cortical elasticity. These studies support the hypothesis that the regulation of cell adhesion is coordinated with contraction and demonstrate the dynamic nature of cell adhesion to the ECM. It is proposed that coordination of adhesion and VSMC contraction is an important mechanism that allows for an efficient transfer of force between the contractile apparatus of the cell and the extracellular environment.