α5β1 integrin-fibronectin interactions specify liquid to solid phase transition of 3d cellular aggregatesα5β1 integrin-fibronectin交互指定液体到固体相变的3 d细胞聚集体.pdfVIP

a5b1 Integrin-Fibronectin Interactions Specify Liquid to Solid Phase Transition of 3D Cellular Aggregates 1 1 2 Carlos E. Caicedo-Carvajal , Troy Shinbrot , Ramsey A. Foty * 1 Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, United States of America, 2 Department of Surgery, University of Medicine and Dentistry, New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America Abstract Background: Tissue organization during embryonic development and wound healing depends on the ability of cells on the one hand to exchange adhesive bonds during active rearrangement and on the other to become fixed in place as tissue homeostasis is reached. Cells achieve these contradictory tasks by regulating either cell-cell adhesive bonds, mediated by cadherins, or cell-extracellular matrix (ECM) connections, regulated by integrins. Integrin a5b1 and soluble fibronectin (sFN) are key players in cell-ECM force generation and in ECM polymerization. Here, we explore the interplay between integrin a5b1 and sFN and its influence on tissue mechanical properties and cell sorting behavior. Methodology/Principal Findings: We generated a series of cell lines varying in a5b1 receptor density. We then systematically explored the effects of different sFN concentrations on aggregate biomechanical properties using tissue surface tensiometry. We found previously unreported complex behaviors including the observation that interactions between fibronectin and integrin a5b1 generates biphasic tissue cohesion profiles. Specifically, we show that at constant sFn concentration, aggregate cohesion increases linearly as a5b1 receptor density is increased from low to mod