Functional consequences of plasmalogens - Membrane curvature and lipid miscibility

缩醛磷脂的功能后果 - 膜曲率和脂质混溶性

基本信息

批准号：
10452272
负责人：
Alison Leonard
金额：
$ 0.25万
依托单位：
UNIVERSITY OF DELAWARE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-30 至 2021-08-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10452272
关键词：
Address Affect Alzheimer&apos s Disease Anabolism Asthma Binding Biological Biological Assay Biological Models Biophysics Brain Caveolins Cell membrane Cells Cellular biology Chemicals Cholesterol Complex Coupling Data Development Endocytosis Esters Eye Fellowship Fluorescence Microscopy Fluorescence Resonance Energy Transfer Glycerol Goals Health Heart Higher Order Chromatin Structure Homeostasis Human Image Impairment Individual Investigation Kidney Kinetics Knowledge Letters Link Lipids Liquid substance Liver Lung Membrane Membrane Fluidity Membrane Fusion Modeling National Institute of Child Health and Human Development Nerve Tissue Pathway interactions Phase Phosphatidylethanolamine Phospholipids Physiological Plasmalogens Prevalence Property Research Role Series Signal Transduction Structure Tail Temperature Testing Theoretical model Training Transmembrane Transport Unsaturated Fats Vertebral column Vesicle Work base biophysical properties direct application ethanolamine plasmalogens experimental study graduate student lipid transport lipidomics melting models and simulation molecular dynamics peroxisome preference pressure saturated fat simulation skills trafficking vinyl ether

项目摘要

Abstract. Functional consequences of plasmalogens—Membrane curvature and lipid miscibility Phosphatidylethanolamine plasmalogen (PEp) is prevalent in mammalian membranes, comprising 20 mol% of phospholipids in the inner leaflet of the plasma membrane (PM) according to recent lipidomics. Despite its prevalence, surprisingly little is known about its biophysical effects on biological membranes. The chemically unique vinyl ether linkage between the glycerol backbone and sn-1 fatty acyl chain is known to increase membrane fluidity and curvature; yet, PEp partitions into more structured cholesterol rich regions of the plasma membrane. Its unique curvature properties and roles in endocytic pathways and cellular signaling suggest it disrupts membrane integrity to promote fusion and fission. The proposed research combines all-atom molecular dynamics (MD) with FRET imaging and membrane fusion assays to quantify the curvature properties of pure PEp and characterize biologically relevant PEp mixtures. The proposal is for an F32 individual training fellowship. As a graduate student, trainee Dr. Alison Leonard (AL) developed an all-atom force field for PEp which she will use in the MD simulations. Whereas AL's graduate research focused on the development of lipid force field parameters and modeling of single-component membranes, the central hypothesis of this proposal addresses a topic with direct application to human health, the mechanisms of lipid homeostasis. AL will expand her knowledge of cell biology and theoretical modeling of biologically relevant lipid mixtures.

抽象的。浆元的功能后果 - 膜曲率和脂质混杂性磷脂酰乙醇胺血浆原（PEP）在哺乳动物膜中普遍存在，质膜内部小叶中的20摩尔％的磷脂（PM）尽管普遍存在，但对它对生物膜的生物物理作用。化学独特的乙烯基醚已知甘油主链和SN-1脂肪酰基链之间的连接会增加膜的流动性和曲率；然而，佩普分区分为更结构化的胆固醇质膜的丰富地区。其独特的曲率特性和角色内吞通路和细胞信号传导表明它破坏了膜完整性促进融合和裂变。提出的研究结合了全原子分子具有FRET成像和膜融合测定的动力学（MD），以量化纯PEP的曲率特性并表征了与生物学相关的PEP混合物。该提议是针对F32个人培训奖学金的。作为研究生，学员艾莉森·伦纳德（Alison Leonard）博士（AL）开发了PEP的全原子力场，她将使用该领域 MD模拟。而AL的研究生研究重点是发展脂质力场参数和单组分膜的建模，中央该提案的假设涉及直接应用人类健康的主题，脂质稳态的机制。 Al将扩大她对细胞生物学的了解和生物学相关脂质混合物的理论建模。