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

囊泡是由脂质双层膜包裹的液体囊组成的亚细胞室。它们在分子运输等细胞过程中起着关键作用。合成囊泡通常用于工业应用，如药物输送和个人护理产品。例如，混合成分膜的小囊泡（脂质纳米颗粒）已被用于增强mRNA疫苗跨细胞边界的递送。大多数具有实际意义的囊泡由具有多种脂质成分和/或蛋白质的双层组成，这些成分或以混合良好的流体状态存在，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和膜出芽的蛋白质集中中起着重要作用。然而，当囊泡在生理情况下或在制造过程中悬浮在流动中时，这种相行为是如何受到影响的，人们知之甚少。由于膜张力的变化和脂质重排的能量学，流动引起的变形影响了这类系统的相变。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脂质结构域形成的热力学和动力学。该项目的结果将揭示囊泡组成如何影响流动中的膜变形和破裂，这对于以可控的高通量方式制造囊泡（包括mRNA疫苗）的生物医学应用变得越来越重要。实验和边界元模拟将用于研究精确定义流下多组分囊泡的行为。通过在被称为Stokes陷阱的微流体装置中直接观察具有良好控制成分的囊泡，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系绳从囊泡膜中拔出的流动不稳定性，此外还将清楚地了解相分离如何改变这种不稳定性的关键条件。模拟将特别提供关于流动引起的变形、脱混和膜弯曲时间尺度如何相互竞争的定量信息，以确定囊泡的不均匀拉伸和系绳的挤压。研究团队将为伊利诺伊州的Cena y Ciencias项目（“晚餐与科学”）创建活动，该项目每月在当地小学举办一次科学之夜，让K-5学生和他们的家人了解聚合物、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，该博物馆每年有2万名游客。该奖项反映了美国国家科学基金会的法定使命，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。

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.