Binding forces of hepatic microsomal and plasma membrane proteins in normal and pancreatitic rats: An AFM force spectroscopic study

The docking and fusion of membrane-bound vesicles at the cell plasma membra ne are brought about by several participating vesicle membrane, plasma memb rane, and soluble cytosolic proteins. An understanding of the interactions between these participating proteins will provide an estimate of the potenc y and efficacy of secretory vesicle docking and fusion at the plasma membra ne in cells of a given tissue. Earlier studies suggest that in chronic panc reatitis, glucose intolerance may be associated with impaired exocytosis/en docytosis of hepatic insulin receptor and glucose transporter proteins. In this study, the binding force profiles between microsome membrane proteins and plasma membrane proteins in liver obtained from normal and pancreatitic rats have been examined using atomic force microscopy. The ability of a VA MP-specific antibody to alter binding between microsome- and plasma membran e-associated membrane proteins was examined. In pancreatitic livers, a sign ificant loss in microsome-plasma membrane binding is observed. Furthermore, our study shows that, in contrast to control livers, the microsome-plasma membrane binding in pancreatitic livers is VAMP-independent, which suggests an absence of VAMP participation in membrane-microsome binding. In confirm ation with our earlier findings, these studies suggest altered membrane rec ycling in liver of rats with chronic pancreatitis. (C) 1999 Wiley-Liss, Inc .