GOALI: Vesicle Dynamics: The Transition From Unilamellar to Multilamellar Structures

0968105-基于LealVesicle的家庭和个人护理产品在全球范围内构成了数十亿美元的业务。此外，利用囊泡包装和运输药物或其他化学物质的产品提供了刚刚开始开发的巨大潜力。然而，对决定囊泡结构的因素缺乏基本的了解，这不仅在产品稳定性方面代价高昂，而且限制了新的和更有效的包埋程序的开发。这里提出的研究是朝着解决非常重要的一类阳离子脂质双层囊泡的这一缺陷迈出的非常重要的第一步。观察到这种囊泡既存在于单层结构中，也存在于多层(洋葱)结构中，有时会自发地从单层结构转变为多层结构，时间长达数小时或数天。这个项目的目的是了解囊泡的结构可能如何以及何时可能从单一的双层膜改变(或改变)为涉及多个嵌入的双层的所谓的“洋葱”结构。将进行实验，以将对囊泡结构的观察及其随时间的变化与膜的机械性能的测量相关联。膜的性质将通过不同的脂类/表面活性剂组合来改变，并且脂类的总浓度将被改变以控制悬浮液中囊泡的体积分数。囊泡结构将主要通过冷冻-透射电子显微镜成像进行研究。膜的性质将通过使用巨大的单层囊泡的微吸管吸入技术来确定。此外，还将利用数值模拟方法，从分子动力学和连续介质的角度，为预测囊泡结构的变化提供理论基础。因此，这里提出的实验和理论的结合将为双层膜的组成、其可测量的机械性能和相应的囊泡结构之间的关系提供新的见解。这项拟议的研究具有变革性，因为它是使结构可控的囊泡设计合理化的第一步，在这两种材料开发中都有应用，可能在药物输送过程中也是如此。事实上，我们的工业合作伙伴认为这个项目具有长期潜力，可以“以革命性的方式改变他们的研究策略”。此外，它量化了用于膜性质测量的微吸管吸入法；它提高了通过基于连续介质的模型从理论上描述囊泡的能力。更广泛的影响：博士生将从与宝洁的合作中受益匪浅，除了获得UCSB现有的材料和设施外，还将获得开放文献中无法获得的关于囊泡工业配方和生产的洞察力。该项目还涉及重要的外联活动，包括：1)与Todd Squires一起举办UCSB大一新生研讨会(面向非理科专业学生)，讨论各种食品和个人护理产品(包括由囊泡制成的产品)中的科学和工程问题；以及2)资助PI参加由UCSB的MSERC项目赞助的暑期本科和教师实习生项目。这些项目对于学生来说是一个绝佳的机会，他们需要8-10周的个人指导的暑期研究项目，以及每周与教育人员举行的会议，以培养口语、视觉和书面沟通技能。

0968105 - LealVesicle based home and personal care products constitute a multi-billion dollar business worldwide. Further, products that utilize vesicles for the encapsulation and transport of drugs or other chemical species offer an enormous potential that is only beginning to be exploited. Yet a fundamental understanding of what determines vesicle structure is lacking, and this is both extremely costly in terms of product stability, and limiting in the development of new and more effective encapsulation procedures. The research proposed here is a very significant first step toward addressing this deficiency for the very important class of cationic lipid bilayer vesicles. Such vesicles are observed to exist both in unilamellar and multilamellar ("onion") structures, with a transition from unilamellar to multilamellar structures sometimes occurring spontaneously over periods of hours or days. This project is aimed at understanding how and when the structure of vesicles may change (or be changed) from a single bilayer membrane to so-called "onion" structures involving multiple imbedded bilayers. Experiments will be done to correlate observations of vesicle structure, and how it may change with time, with measurements of the mechanical properties of the membrane. Membrane properties will be varied via different combinations of lipids/surfactants, and the total concentration of lipids will be changed to control the volume fraction of vesicles in the suspension. Vesicle structure will be studied primarily via Cryo-TEM imaging. Membrane properties will be determined via micropipette aspiration techniques using giant unilamellar vesicles. A theoretical basis will also be developed, using numerical simulation methods, for predicting the changes of vesicle structure, both from a molecular dynamics and continuum point of view. The combination of experiments and theory proposed here will therefore provide new insight into the relationship between the constituent make-up of bilayer membranes, their measurable mechanical properties, and the structure of corresponding vesicles. The proposed research is transformative as it is a first step in rationalizing the design of vesicles with control over structure with applications in both materials development, and potentially in drug delivery processes. Indeed, our industrial partner views this project as having the long term potential for changing their "research tactics in a revolutionary way". In addition, it quantifies the micropipette aspiration method for the measurement of membrane properties; and it improves the ability to theoretically describe vesicles via continuum-based models. Broader Impacts: The PhD student will benefit greatly from collaboration with Procter and Gamble via access to a broad range of materials, and facilities, beyond what is available at UCSB, as well as a level of insight about the industrial formulation and production of vesicles, that is simply not available in the open literature. The project also involves important outreach activities including: 1) the development (together with Todd Squires) of a UCSB freshman seminar (for non-science majors) on the science and engineering that goes into various food and personal care products, including those made from vesicles; and 2) funding to allow participation of the PI in the summer undergraduate and teacher intern programs sponsored by the MSERC program at UCSB. These programs are a fantastic opportunity for students involving 8-10 week individually mentored summer research projects, as well as weekly meetings with education staff to develop oral, visual and written communication skills.