Suppression of Cell Traction Force and Enhanced Force Polarity are Key Factors in Vascular Smooth Muscle Cell Differentiation Induced by Low Serum Culture
Vascular smooth muscle cells (VSMCs) in the arterial walls play important roles in regulating vascular contraction and dilation. VSMCs actively remodel the arterial walls and dedifferentiate from the contractile to the synthetic phenotype under pathological conditions. The mechanism underlying phenotypic transition of VSMCs is important for understanding its role in the pathophysiology of disease. Although numerous studies have reported various biochemical pathways that stimulate the phenotypic transition of VSMCs, very little is known about relation between their phenotypic transition and cellular traction force, which affects many cellular functions. In this study, we induced the differentiation of cultured VSMCs from the synthetic to the contractile phenotype by a low-serum cultivation and investigated changes in the cell traction forces using traction force microscopy technique. The expression of α-SMA, a contractile phenotype marker protein, was significantly upregulated with maturation of actin stress fibers in the low-serum culture, indicating VSMC differentiation was promoted in our experiments. The cells changed their morphology to an elongated bipolar shape, and the direction of the cell traction forces tended to align in the direction of the cell’s major axis. Despite the promotion of contractile differentiation in VSMCs, the overall cell traction forces were significantly reduced, indicating that excessive cell mechanical tension, which might induce cell proliferation and migration, was suppressed during contractile differentiation. These results suggest that suppression of cell traction force and enhanced force polarity might be key factors in VSMC differentiation induced by low serum culture.
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