Biophysical principles of liquid-liquid crystal phase transition in macrophage lipid droplets

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K13521
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 13040:Biophysics, chemical physics and soft matter physics-related
• Research Institution: Kyoto University (2022); Japan Agency for Marine-Earth Science and Technology (2018-2019)
• Principal Investigator: Shimobayashi Shunsuke 京都大学, iPS細胞研究所, 准教授 (50787124)
• Project Period (FY): 2021-11-01 – 2023-03-31
• Keywords: 相転移 / 液晶 / 脂肪滴 / オルガネラ / ソフトマター

Outline of Final Research Achievements

Lipid droplets are cytoplasmic microscale organelles involved in energy homeostasis and handling of cellular lipids and proteins. The core structure is mainly composed of two kinds of neutral lipids, triglycerides and cholesteryl　esters, which are coated by a phospholipid monolayer and proteins. Despite the liquid crystalline nature of cholesteryl esters, the connection between the　lipid composition and physical states is poorly understood. Here, we present a universal intracellular phase diagram of lipid droplets, semiquantitatively consistent with the in vitro phase diagram, and reveal that cholesterol esters cause the liquid-liquid crystal phase transition under near-physiological conditions. We moreover combine in vivo and in vitro studies, together with the theory of confined liquid crystals, to suggest that the radial molecular alignments in the liquid crystallized lipid droplets are caused by an anchoring force at the droplet surface.

Free Research Field

生物物理

Academic Significance and Societal Importance of the Research Achievements

マクロファージで見られる脂質の異常蓄積は、動脈硬化の主要な要因とされています。マクロファージの脂肪滴で多いとされるコレステロールエステルが脂肪滴の相転移を誘導することを見出した本研究は、動脈硬化の予防や治療に向けた新たな戦略を模索する可能性を秘めており、その社会的意義も極めて大きいと言えます。今後より生体内に近い条件での脂質蓄積過程が解明されることが期待でき、その学術的価値はますます高まっていくものと考えられます。