Research Spotlight: Membrane Curvature Catalyzes Lipid Droplet Assembly

Posted on October 16, 2021

Lipid Droplets

Lipid droplets (LDs) aren’t just balls of fat. LDs are organelles that have multiple functions inside cells. These droplets have been studied extensively and have been shown to be at the center of cellular energy metabolism. LDs are composed of a neutral lipid core, either triacylglycerols and/or sterol esters, and a phospholipid monolayer containing proteins. The process of formation for these balls of fat isn’t fully understood. So, Elina Ikonen and her research team at the University of Helsinki, Finland aimed to further investigate this process.

LDs are known to form through a cascade of biochemical and biophysical reactions located at the endoplasmic reticulum (ER). Conditions that favor lipid storage set off a series of biochemical reactions that mediate the production of neutral lipids. The neutral lipids form oil molecules that are encapsulated in the phospholipid bilayer between ER leaflets and are then diffused within the ER. The process by which the neutral lipids separate from the phospholipid bilayer is termed nucleation. There are several physicochemical characteristics of the phospholipid ER membrane that influence the formation and nucleation of LDs. Some of these properties include phospholipid composition, membrane tension, shape, as well as proteins bound to the surface of the forming LDs.

Previous studies have shown that higher membrane surface tension can impede the assembly of LDs and promotes larger LDs. The nucleation process and how it is affected by the physicochemical properties of the membrane are not well understood. Many proteins affect the size and quantity of LD assembly and research has shown that no one protein is indispensable for this process. However, there is one protein that has been implicated as a key factor in the assembly of LDs – seipin. The dysfunction of seipin has been linked to severe forms of lipodystrophy and neurological disorders. In the absence of seipin, a phenotype of few super-sized and many tiny LDs appears. It is important that a cell be able to control the formation of these LDs and a better understanding of this process is important to treat conditions caused by inefficient LD assembly.

Dr. Ikonen and her team were able to give some key insights into the LD assembly process in the ER. They found that membrane curvature decreases the energy barrier needed for the assembly, nucleation, and condensation of neutral lipid molecules. The curvature of a membrane affects the chemical potential of triglyceride molecules. Higher curvature increases the chemical potential of the triglyceride molecules and decreases the energy gap to nucleation barrier. Thus, higher levels of membrane curvature catalyzes LD nucleation at tubules. Furthermore, higher curvature should also increase the frequency of appearance of unstable triglyceride clusters that transit into stable, nascent LDs. This process would lead to uncontrolled LD assembly.

So, how does the body control this process? That’s where the seipin protein comes into play. Seipin appears to dictate where LDs form and controls the number of LD assembly events on tubules. By controlling the transition of some triglyceride clusters into nascent LDs, seipin guarantees that only seipin-positive triglyceride clusters are stabilized and grow. Without seipin, these triglyceride clusters are not regulated and form nascent LDs uncontrollably.

Dr. Ikonen and her team have presented great work that furthers our understanding of how ER topology affects LD assembly. We appreciate the great work being done in her lab and can’t wait to see what other fascinating studies they conduct using Avanti lipids.

To view the full research article, click HERE!

And to check out Avanti’s Headgroup Functionalized Phospholipids or Fluorescent Sterols used for this work, click the links!