Collaborative Research: Dynamics and Stability of Multi-Component Lipid Vesicles in Flow

合作研究：多组分脂质囊泡流动的动力学和稳定性

• 批准号: 2147559
• 负责人: Vivek Narsimhan
• 金额: $ 22.29万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-15 至 2024-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2147559&HistoricalAwards=false
• 关键词: Collaborative; Research; Dynamics; Stability; Multi

Vesicles are sub-cellular compartments consisting of sacs of fluid enclosed by a lipid bilayer membrane. They play a key role in several cellular processes such as molecular trafficking. Synthetic vesicles are often used in industrial applications such as drug delivery and personal care products. For example, small vesicles (lipid nanoparticles) with mixed-composition membranes have been used to enhance delivery of mRNA vaccines across cell boundaries. Most vesicles of practical importance consist of a bilayer with multiple lipid components and/or proteins that exist either in a well-mixed fluid state or with phase-separated domains enriched in protein. This complex phase behavior plays a major role in concentrating proteins for signaling and membrane budding. However, little is known about how this phase behavior is affected when vesicles are suspended in a flow in physiological situations or in manufacturing processes. Flow-induced deformation affects the phase transitions of such systems due to changes in membrane tension and energetics of lipid rearrangement. This work will provide the first quantitative study of how flow-induced tension alters the thermodynamics and kinetics of lipid domain formation for multicomponent membranes. Results from the project will reveal how vesicle composition affects membrane deformation and breakup in flow, which is becoming increasingly important for manufacturing vesicles in a controlled, high-throughput fashion for biomedical applications including mRNA vaccines.Experiments and boundary element simulations will be used to study the behavior of multicomponent vesicles under precisely defined flows. By directly visualizing vesicles with well controlled compositions inside a microfluidic device known as a Stokes trap, this study will explore how external flow alters the kinetics and thermodynamics of phase separation in multicomponent membranes, and in turn, how these behaviors affect vesicle shape and conformation. Both simulations and experiments will quantify flow instabilities in which thin tethers pull out from vesicle membranes, in addition to providing a clear understanding of how phase separation alters the critical conditions for such instabilities. The simulations will in particular provide quantitative information on how flow-induced deformation, de-mixing, and membrane bending timescales compete to determine the non-uniform stretching of vesicles and the extrusion of tethers. The research team will create events for the Cena y Ciencias program (“Supper and Science”) at Illinois, which brings K-5 students and their families to a monthly science night at local elementary schools to learn about soft materials such as polymers, biomaterials, and organic electronics. At Purdue, science demonstrations will be performed about complex fluids and interfacial science for local elementary school students. These events will be repurposed as exhibits for a local science museum that has 20,000 annual visitors.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

囊泡是由脂质双层膜包围的液囊组成的亚细胞区室。 它们在分子运输等多种细胞过程中发挥着关键作用。 合成囊泡通常用于工业应用，例如药物输送和个人护理产品。 例如，具有混合成分膜的小囊泡（脂质纳米颗粒）已被用来增强 mRNA 疫苗跨细胞边界的递送。大多数具有实际重要性的囊泡由具有多种脂质成分和/或蛋白质的双层组成，这些脂质成分和/或蛋白质以充分混合的流体状态存在或具有富含蛋白质的相分离结构域。这种复杂的相行为在信号传导和膜出芽的蛋白质浓缩中发挥着重要作用。 然而，当囊泡在生理情况或制造过程中悬浮在流动中时，这种相行为会受到怎样的影响，人们知之甚少。 由于膜张力和脂质重排能量的变化，流动引起的变形会影响此类系统的相变。这项工作将首次定量研究流动引起的张力如何改变多组分膜的脂质域形成的热力学和动力学。 该项目的结果将揭示囊泡成分如何影响流动中的膜变形和破裂，这对于以受控、高通量方式制造囊泡以用于生物医学应用（包括 mRNA 疫苗）变得越来越重要。实验和边界元模拟将用于研究多组分囊泡在精确定义的流动下的行为。通过直接观察被称为斯托克斯陷阱的微流体装置内成分受到良好控制的囊泡，本研究将探索外部流动如何改变多组分膜中相分离的动力学和热力学，以及这些行为如何影响囊泡的形状和构象。模拟和实验都将量化细线从囊泡膜中拉出的流动不稳定性，此外还可以清楚地了解相分离如何改变这种不稳定性的关键条件。该模拟将特别提供有关流动引起的变形、分层和膜弯曲时间尺度如何竞争以确定囊泡的不均匀拉伸和系链的挤出的定量信息。 研究团队将为伊利诺伊州的 Cena y Ciencias 计划（“晚餐与科学”）举办活动，该计划让 K-5 学生及其家人每月在当地小学参加科学之夜，了解聚合物、生物材料和有机电子等软材料。在普渡大学，将为当地小学生进行有关复杂流体和界面科学的科学演示。 这些活动将被重新用作当地科学博物馆的展品，每年有 20,000 名游客。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。