Multi-cellular Morphogenesis Derived by Interstitial Flow

Biomechanical stimuli derived by interstitial flow regulate morphogenesis of multicellular systems including both physiological and pathological cells. For example, hepatocytes construct three-dimensional structures in directional interstitial flow conditions. Protrusions of tumor cells are also induced by interstitial flow, resulting in enhanced tumor cell invasion. Interestingly, the direction of tumor cell invasion in response to directional interstitial flow differs depending on the type of tumor cells. Furthermore, endothelial cells form capillary networks against the direction of interstitial flow in a magnitude-dependent manner. Taken together, interstitial flow is an important factor for regulating morphogenesis of multicellular systems.