Cargando…

Capturing the Liquid-Crystalline Phase Transformation: Implications for Protein Targeting to Sterol Ester-Rich Lipid Droplets

Lipid droplets are essential organelles that store and traffic neutral lipids. The phospholipid monolayer surrounding their neutral lipid core engages with a highly dynamic proteome that changes according to cellular and metabolic conditions. Recent work has demonstrated that when the abundance of s...

Descripción completa

Detalles Bibliográficos
Autores principales: Braun, R. Jay, Swanson, Jessica M. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9607156/
https://www.ncbi.nlm.nih.gov/pubmed/36295707
http://dx.doi.org/10.3390/membranes12100949
_version_ 1784818471585972224
author Braun, R. Jay
Swanson, Jessica M. J.
author_facet Braun, R. Jay
Swanson, Jessica M. J.
author_sort Braun, R. Jay
collection PubMed
description Lipid droplets are essential organelles that store and traffic neutral lipids. The phospholipid monolayer surrounding their neutral lipid core engages with a highly dynamic proteome that changes according to cellular and metabolic conditions. Recent work has demonstrated that when the abundance of sterol esters increases above a critical concentration, such as under conditions of starvation or high LDL exposure, the lipid droplet core can undergo an amorphous to liquid-crystalline phase transformation. Herein, we study the consequences of this transformation on the physical properties of lipid droplets that are thought to regulate protein association. Using simulations of different sterol-ester concentrations, we have captured the liquid-crystalline phase transformation at the molecular level, highlighting the alignment of sterol esters in alternating orientations to form concentric layers. We demonstrate how ordering in the core permeates into the neutral lipid/phospholipid interface, changing the magnitude and nature of neutral lipid intercalation and inducing ordering in the phospholipid monolayer. Increased phospholipid packing is concomitant with altered surface properties, including smaller area per phospholipid and substantially reduced packing defects. Additionally, the ordering of sterol esters in the core causes less hydration in more ordered regions. We discuss these findings in the context of their expected consequences for preferential protein recruitment to lipid droplets under different metabolic conditions.
format Online
Article
Text
id pubmed-9607156
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-96071562022-10-28 Capturing the Liquid-Crystalline Phase Transformation: Implications for Protein Targeting to Sterol Ester-Rich Lipid Droplets Braun, R. Jay Swanson, Jessica M. J. Membranes (Basel) Article Lipid droplets are essential organelles that store and traffic neutral lipids. The phospholipid monolayer surrounding their neutral lipid core engages with a highly dynamic proteome that changes according to cellular and metabolic conditions. Recent work has demonstrated that when the abundance of sterol esters increases above a critical concentration, such as under conditions of starvation or high LDL exposure, the lipid droplet core can undergo an amorphous to liquid-crystalline phase transformation. Herein, we study the consequences of this transformation on the physical properties of lipid droplets that are thought to regulate protein association. Using simulations of different sterol-ester concentrations, we have captured the liquid-crystalline phase transformation at the molecular level, highlighting the alignment of sterol esters in alternating orientations to form concentric layers. We demonstrate how ordering in the core permeates into the neutral lipid/phospholipid interface, changing the magnitude and nature of neutral lipid intercalation and inducing ordering in the phospholipid monolayer. Increased phospholipid packing is concomitant with altered surface properties, including smaller area per phospholipid and substantially reduced packing defects. Additionally, the ordering of sterol esters in the core causes less hydration in more ordered regions. We discuss these findings in the context of their expected consequences for preferential protein recruitment to lipid droplets under different metabolic conditions. MDPI 2022-09-28 /pmc/articles/PMC9607156/ /pubmed/36295707 http://dx.doi.org/10.3390/membranes12100949 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Braun, R. Jay
Swanson, Jessica M. J.
Capturing the Liquid-Crystalline Phase Transformation: Implications for Protein Targeting to Sterol Ester-Rich Lipid Droplets
title Capturing the Liquid-Crystalline Phase Transformation: Implications for Protein Targeting to Sterol Ester-Rich Lipid Droplets
title_full Capturing the Liquid-Crystalline Phase Transformation: Implications for Protein Targeting to Sterol Ester-Rich Lipid Droplets
title_fullStr Capturing the Liquid-Crystalline Phase Transformation: Implications for Protein Targeting to Sterol Ester-Rich Lipid Droplets
title_full_unstemmed Capturing the Liquid-Crystalline Phase Transformation: Implications for Protein Targeting to Sterol Ester-Rich Lipid Droplets
title_short Capturing the Liquid-Crystalline Phase Transformation: Implications for Protein Targeting to Sterol Ester-Rich Lipid Droplets
title_sort capturing the liquid-crystalline phase transformation: implications for protein targeting to sterol ester-rich lipid droplets
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9607156/
https://www.ncbi.nlm.nih.gov/pubmed/36295707
http://dx.doi.org/10.3390/membranes12100949
work_keys_str_mv AT braunrjay capturingtheliquidcrystallinephasetransformationimplicationsforproteintargetingtosterolesterrichlipiddroplets
AT swansonjessicamj capturingtheliquidcrystallinephasetransformationimplicationsforproteintargetingtosterolesterrichlipiddroplets