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体囊组成的亚细胞区室。 它们在几个细胞过程中发挥关键作用，如分子运输。 合成囊泡通常用于工业应用，如药物递送和个人护理产品。 例如，具有混合组合物膜的小囊泡（脂质纳米颗粒）已被用于增强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组分和/或蛋白质的双层组成，所述脂质组分和/或蛋白质以充分混合的流体状态或具有富含蛋白质的相分离结构域存在。这种复杂的相行为在浓缩蛋白质用于信号传导和膜出芽中起着重要作用。 然而，很少有人知道如何影响这种相行为时，囊泡悬浮在生理情况下或在生产过程中的流动。 流动引起的变形影响相变的系统，由于膜张力和能量的脂质重排的变化。这项工作将提供第一个定量研究如何流动引起的张力改变的热力学和动力学的脂质结构域形成的多组分膜。 该项目的结果将揭示囊泡的组成如何影响膜的变形和破裂的流动，这是越来越重要的制造囊泡在一个可控的，高通量的生物医学应用，包括mRNA vaccine.Experiments和边界元模拟将被用来研究精确定义的流量下的多组分囊泡的行为。通过直接可视化囊泡与良好控制的组合物内的微流控装置称为斯托克斯陷阱，本研究将探讨外部流动如何改变动力学和热力学相分离的多组分膜，反过来，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流动不稳定性，其中薄系链从囊泡膜中拉出，除了提供一个清晰的理解如何相分离改变这种不稳定性的临界条件。模拟将特别提供关于流动诱导的变形、分层和膜弯曲时间尺度如何竞争以确定囊泡的非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”）创建活动，该计划将K-5学生及其家人带到当地小学的每月科学之夜，以了解聚合物，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关于复杂流体和界面科学的科学演示。 这些活动将被重新利用为当地科学博物馆的展品，该博物馆每年有20，000名参观者。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。