Surface tension-driven sorting of human perilipins on lipid droplets

Abstract

Perilipins (PLINs), the most abundant proteins on lipid droplets (LDs), display similar domain organization including amphipathic helices (AH). However, the five human PLINs bind different LDs suggesting different modes of interaction. We established a minimal system whereby artificial LDs covered with defined polar lipids were transiently deformed to promote surface tension. Binding of purified PLIN3 and PLIN4 AH was dependent on tension, even with polar lipids favoring packing defects, and showed an inverse correlation between protein and phospholipid densities on LDs. In contrast, PLIN1 bound readily to LDs fully covered by phospholipids; PLIN2 showed an intermediate behavior. In human adipocytes, PLIN3/4 were found in a soluble pool and relocated to LDs upon stimulation of triglyceride synthesis, whereas PLIN1 and PLIN2 localized to pre-existing LDs, consistent with the huge difference in LD avidity observed in vitro. We conclude that the PLIN repertoire is adapted to handling LDs with different surface properties.