Hepatocyte adhesion to immobilized carbohydrates. I. Sugar recognition is followed by energy-dependent strengthening.

Cell-cell recognition and adhesion are thought to be complex, multistep phenomena, and may involve cell surface carbohydrates and their receptors on apposing cell surfaces. We have modeled such interactions using hepatocytes and polymer (gel) surfaces derivatized with carbohydrate ligands, and have demonstrated carbohydrate-specific cell adhesion (Schnaar, R. L., Weigel, P. H., Kuhlenschmidt, M. S., Lee, Y. C., and Roseman, S. (1978) J. Biol. Chem. 253, 7940-7951). In the present studies, we have developed a method to quantitate the forces involved in cell-gel adhesion. Our method is based on that of McClay et al. (McClay, D. R., Wessel, G. M., and Marchase, R. B. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 4975-4979) which was designed to measure the forces involved in intercellular adhesion. The following results were obtained. 1) Chicken and rat hepatocytes adhere specifically to gels derivatized with N-acetylglucosamine and galactose, respectively, at either 4 degrees C or 37 degrees C. 2) At 37 degrees C, after a lag of 10-20 min, stabilization of the adhesion occurs, resulting in a 15-fold (or greater) increase in the force of adhesion. 3) This marked strengthening of adhesion does not occur at 4 degrees C and is blocked by inhibitors of oxidative phosphorylation. These data demonstrate that cells can recognize and adhere to specific carbohydrates on apposing surfaces, and can then respond by mobilizing cellular energy to strengthen that adhesion. This series of events is strikingly similar to that shown for cell-cell adhesion between hepatocytes or between neural retina cells (Umbreit, J., and Roseman, S. (1975) J. Biol. Chem. 250, 9360-9368; McClay, D. R., Wessel, G. M., and Marchase, R. B. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 4975-4979). The present results suggest that the cell surface analogs described may provide a well controlled experimental system to probe the molecular events involved in cell-cell adhesion.