Vasoactive agents result in coordinated changes in vascular smooth muscle cell elasticity and extracellular matrix adhesion

Abstract

Coordination of mechanotransduction and force transmission within the blood vessel wall requires a physical adhesion of vascular smooth muscle cells (VSMCs) to extracellular matrix proteins (ECM) and surrounding VSMCs. Our hypothesis was that integrin adhesion to the ECM is dynamically up‐regulated in VSMC during contractile activation and likewise down‐regulated during relaxation to support changes in vessel diameter and wall tension. Real‐time measurements of cell adhesion and cell elasticity were obtained with atomic force microscopy (AFM) in response to angiotensin II (Ang II) and adenosine (Ado). ECM adhesion behavior was evaluated with fibronectin (FN) coated microbead‐tipped (5 μm dia) AFM probes. Single VSMCs were isolated from rat cremaster skeletal muscle arterioles and cultured 3–8 days before AFM experiment. The results show that the administration of Ang II (10−6M) in cell bath immediately increased the strength of adhesion between the AFM probe and cell as well as probability of binding between FN and the cell. Cell stiffness also increased in parallel with adhesion upon Ang II stimulation. In contrast, Ado (10−4M) decreased cell elasticity and the adhesion of integrins to FN. These findings support the hypothesis that a vasoconstrictor can activate through inside‐out mechanisms both the contractile process and cell adhesion to the ECM in a coordinated fashion, while a vasodilator has the opposite effects. The role of the changes in adhesion may be related to altered mechanics or cell signaling involving the focal adhesion sites. (1P01HL095486 to G.A.M. and AHA 0835676N to Z.S.)