We propose to investigate the structural and biochemical characteristics of the surface membrane of human fibroblasts grown in cell culture and membrane mediated changes which occur in plasma low density lipoproteins (LDL) during the early stages of lipid uptake. Surface membranes will be obtained from normal subjects and patients who are heterozygous and homozygous for familial hypercholesterolemia. Our objectives are: 1) lipid composition to determine the kind and amount of neutral lipid, glycosphingolipid and phospholipid; 2) carbohydrate moieties - a) structure - to examine in detail the biochemical characteristics of the carbohydrates of the glycolipids; to isolate and characterize the major glycoprotein of the membrane; b) function - to investigate the role of the carbohydrate moieties in the interaction of membranes and lipoproteins by modifying the carbohydrate components of the membrane and/or LDL and assessing its effect on their binding; 3) protein components - a) to identify by the lactoperoxidase iodination technique the surface proteins and glycoproteins of the cell; b) to determine whether the structural proteins of the membrane share antigenic sites with the plasma lipoproteins; 4) enzymatic modification - to investigate the action of membrane bound enzymes on the lipid and protein components of LDL; 5) ultrastructure - to compare the ultranstructural characteristics of the membranes from normal and mutant cells.