The Department of Biomedicine

BBB seminar: Donald M. Small

How apolipoproteins stabilize lipoprotein interfaces

Main content

Donald M. Small
Department of Physiology and Biophysics, Boston University School of Medicine, Boston, USA

Beta lipoproteins are small aggregates of insoluble lipids (triacylglycerol, cholesterol esters and phospholipids) and apoliproteins which are assembled in cells of the intestine and the liver, secreted into the plasma and deliver various lipids to distant cells where they are used for key metabolic functions in the cells. The insoluble lipids alone form instable droplets and if present in blood would fuse to form very large droplets which would block capillaries. However, the lipids are stabilized as small particles by an interfacial layer of polar phospholipids and apolipoproteins. Apolipoproteins such as apoB are essential for the assembly of triglyceride-rich lipoproteins which transport energy and building blocks around the body. As triglyceride-rich beta lipoproteins enter the plasma they bind soluble apoproteins and then are acted on by lipoprotein lipase which hydrolyzes triglyceride to produce fatty acids and monoacyl glycerides. This reaction results in a decrease in the size of the triaclyglycerol core and an increase in the number of surface molecules which results in an increase in the surface pressure. ApoB and smaller exchangeable apolipoproteins such as apoA-1 are important in giving flexibility and stability during metabolism occurring in plasma. Apolipoprotein B is made up of several superdomains having α or β structure. The apoprotein has considerable flexibility on the surface of lipoproteins and can change the area of hydrophobic surface it covers by up to 50% depending on surface pressure.

We have explored how the various domains of amphipathic alpha helices and amphipathic beta sheets predicted to be present in apoB and apoA-1 behave at the interface as a function of pressure, and based on these studies have developed a model for the interaction of apoB and apoA-1 on triglyceride containing particles. These experiments will indicate why apoB remains with the particle and is nonexchangeable even at very high surface pressure.

Professor Donald M. Small is Chairman of the Department of Physiology and Biophysics at the Boston University School of Medicine. His interests cover the general area of the physical properties of fats and oils, detergents, lipids, proteins and lipid-protein interactions. Specific systems of interest include artificial membranes (bilayers), surfaces and cores of native lipoproteins, and recombinant lipoproteins using specific lipids and either native or genetically engineered apolipoproteins. A biophysical approach is used to probe disease processes such as atherosclerosis, lipoproteinemias and gallstone formation. Recent work includes: (1) physical characterization of stereospecific lipids and fats, (2) physical analysis of recombinant lipoprotein particles and (3) studies of the metabolism of recombinant lipoproteins in whole animals, perfused livers and cell cultures. The mechanisms of progression and regression of atherosclerosis are also being pursued. A wide variety of biophysical, biochemical and physiological methods are used to investigate these problems.

Professor Small has received many prestigious awards. He was an invited lecturer at the Norwegian Biochemical Society's Winter Meeting in 1995.