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

0968105 - LealVesicle的家庭和个人护理产品构成了全球数十亿美元的业务。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，这只是开始被利用。然而，缺乏对决定囊泡结构的因素的基本理解，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开发。这里提出的研究是一个非常重要的第一步，解决这一缺陷的非常重要的一类阳离子脂质双层囊泡。观察到这种囊泡以单层和多层（“洋葱”）结构存在，有时在数小时或数天内自发地发生从单层到多层结构的转变。 该项目旨在了解囊泡的结构如何以及何时可能从单个双层膜改变（或改变）为涉及多个嵌入双层的所谓“洋葱”结构。实验将进行相关的观察囊泡结构，以及它如何随时间变化，与测量的机械性能的膜。膜特性将通过脂质/表面活性剂的不同组合而变化，并且脂质的总浓度将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Cryo-TEM成像进行研究。将使用巨大单层囊泡通过微量移液管抽吸技术测定膜性质。也将开发的理论基础，使用数值模拟方法，预测囊泡结构的变化，无论是从分子动力学和连续的观点。 因此，这里提出的实验和理论的结合将提供新的见解的双层膜，其可测量的机械性能，和相应的囊泡的结构的组成之间的关系。拟议的研究是变革性的，因为它是合理化囊泡设计的第一步，可以控制结构，应用于材料开发和潜在的药物递送过程。事实上，我们的工业合作伙伴认为这个项目具有长期的潜力，可以改变他们的“革命性的研究策略”。此外，它量化了用于测量膜特性的微量吸管抽吸方法;并且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： 博士生将从与宝洁公司的合作中受益匪浅，通过获得广泛的材料和设施，超出了UCSB的可用范围，以及对工业配方和囊泡生产的深入了解，这在公开文献中根本不可用。 该项目还涉及重要的外展活动，包括：1）开发（与托德斯奎尔斯一起）UCSB新生研讨会（针对非科学专业），讨论各种食品和个人护理产品的科学和工程，包括由囊泡制成的产品;以及2）资助PI参与UCSB MSRC计划赞助的夏季本科生和教师实习计划。这些课程是学生参与8-10周单独指导的夏季研究项目的绝佳机会，以及与教育工作人员每周举行会议，以发展口头，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.