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

[0968105]以LealVesicle为基础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，利用囊泡封装和运输药物或其他化学物质的产品提供了巨大的潜力，而这只是刚刚开始被开发。然而，对什么决定囊泡结构的基本理解是缺乏的，这在产品稳定性方面是极其昂贵的，并且限制了新的和更有效的封装程序的发展。这里提出的研究是解决这一缺陷的非常重要的第一步，为非常重要的一类阳离子脂质双分子层囊泡。观察到这种囊泡存在于单层和多层（“洋葱”）结构中，有时在数小时或数天内自发地从单层结构过渡到多层结构。该项目旨在了解囊泡的结构如何以及何时可能从单一双层膜转变（或被改变）为涉及多个嵌入双层的所谓“洋葱”结构。将进行实验，将囊泡结构的观察，以及它如何随时间变化，与膜的机械性能的测量联系起来。通过脂质/表面活性剂的不同组合可以改变膜的性质，并且通过改变脂质的总浓度来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镜成像进行研究。膜的性质将通过使用巨型单层囊泡的微管抽吸技术来确定。还将利用数值模拟方法，从分子动力学和连续体的角度预测囊泡结构的变化，建立理论基础。因此，本文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。拟议的研究具有变革性，因为它是使囊泡设计合理化的第一步，具有控制结构的功能，可用于材料开发，并可能用于药物输送过程。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，还量化了用于测定膜性能的微移管抽吸法；它提高了通过基于连续体的模型从理论上描述囊泡的能力。更广泛的影响：博士生将从与宝洁公司的合作中受益匪浅，通过访问广泛的材料和设施，超出UCSB提供的，以及对工业配方和囊泡生产的深入了解，这在公开文献中是根本无法获得的。该项目还包括重要的外展活动，包括：1)与托德·斯奎尔斯（Todd Squires）一起，为UCSB的新生（非理工科学生）举办科学与工程研讨会，讨论各种食品和个人护理产品，包括由囊泡制成的产品；2)资助PI参加由UCSB MSERC项目赞助的夏季本科生和教师实习项目。这些项目对学生来说是一个极好的机会，包括8-10周的单独指导的暑期研究项目，以及每周与教育人员的会议，以培养口头，视觉和书面沟通技巧。

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.