CAREER: Understanding the fundamental mechanisms of vesiculation and solute encapsulation of smectic phospholipid films on cellulose

职业：了解纤维素上近晶磷脂膜的囊泡化和溶质封装的基本机制

基本信息

批准号：
1848573
负责人：
Anand Subramaniam
金额：
$ 50.04万
依托单位：
University of California - Merced
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1848573&HistoricalAwards=false
关键词：
CAREER Understanding fundamental mechanisms vesiculation

项目摘要

Non-technical SummaryThis CAREER award will support an integrated research and education plan to understand the assembly of cell-like vesicles from phospholipid layers on cellulose paper. Nature uses membranes to encapsulate biological cells. Understanding the process in nature and then building vesicles that mimic cell membranes is useful. The vesicles can, for example, be used as microscale chemical reactors or as vehicles for encapsulating and controllably releasing therapeutic drugs. The principal investigator (PI) and his students will investigate the effects of physical parameters such as the temperature, the ionic strength of the solution, and the charge density of the phospholipids on vesicle formation. The research team will study the encapsulation of ionic cargo into the vesicles under differing physical conditions. Experimental data that is gathered will be used to build and test analytical and numerical models to better understand the process of formation of vesicles and the process of encapsulating cargo. The award will also support the PI's efforts to enhance the undergraduate and graduate Bioengineering curricula by designing new hands-on laboratory courses. The PI will create a customizable experimental toolkit, the "SynCell Toolkit", that will be implemented in K-12 classrooms to increase interest in biomaterials research. The award will provide opportunities for research experiences for high school, undergraduate, and graduate students in a diverse multidisciplinary environment in the relatively under-served region of Central California.Technical Abstract: Giant vesicles are in vitro constructs that mimic the minimal configuration of biological cells. There is still a lack of a general understanding of the process of vesiculation that leads to giant vesicle formation from surface-supported smectic phospholipid films. This CAREER award will support an integrated research, education, and outreach plan to obtain new knowledge and fundamental insights into the basic process of giant vesicle formation and the encapsulation of solutes in vesicles. A key distinguishing approach of this proposal is the PI's use of a continuum approximation to analyze the evolution of a population of vesicles rather than focusing on analyzing the growth of isolated vesicles. This approach is enabled by two key discoveries in the PI's lab: (1) The discovery of a cellulose-based method for forming giant vesicles, (2) A stopped-growth method for large-scale analysis of images that can characterize the entire population of vesicles from a sample. The PI will achieve his integrated research and educational goals by using a combination of experiments, and analytical and numerical modeling. Research aims include: (1) Understanding the dynamics of vesiculation by studying whole populations of giant vesicles produced on cellulose paper. (2) Deciphering the intermolecular and/or intersurface forces that govern vesiculation by controlled perturbation of double-layer electrostatic forces and membrane undulation forces. (3) Understanding the process of encapsulation of ionic solutes during vesiculation by temporally decoupling the process of growth from the process of loading cargo. The educational and outreach components include: (1) Incorporating laboratory components and new courses designed to foster a mode of inquiry-based learning to the Bioengineering curricula. (2) Developing a customizable "SynCell Toolkit", that will be implemented in K-12 classrooms to encourage K-12 students to pursue careers in STEM. (3) Provide opportunities for research experiences for high school, undergraduate, and graduate students.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.

非技术摘要该职业奖将支持一项综合研究和教育计划，以了解纤维素纸上磷脂层的细胞样囊泡的组装。大自然使用膜来封装生物细胞。了解自然界的过程，然后构建模仿细胞膜的囊泡是有用的。例如，囊泡可以用作微型化学反应器或用作封装和可控释放治疗药物的载体。首席研究员 (PI) 和他的学生将研究温度、溶液离子强度和磷脂电荷密度等物理参数对囊泡形成的影响。研究小组将研究不同物理条件下离子货物封装到囊泡中的情况。收集的实验数据将用于建立和测试分析和数值模型，以更好地了解囊泡的形成过程和封装货物的过程。该奖项还将支持 PI 通过设计新的实践实验室课程来加强本科生和研究生生物工程课程的努力。 PI 将创建一个可定制的实验工具包，即“SynCell 工具包”，该工具包将在 K-12 教室中实施，以提高人们对生物材料研究的兴趣。该奖项将为加州中部服务相对匮乏的地区的高中生、本科生和研究生提供在多样化的多学科环境中获得研究经验的机会。技术摘要：巨型囊泡是模仿生物细胞最小配置的体外构建体。对于导致表面支持的近晶磷脂膜形成巨大囊泡的囊泡形成过程仍然缺乏一般性的了解。该职业奖将支持一项综合研究、教育和推广计划，以获得有关巨型囊泡形成和囊泡中溶质封装的基本过程的新知识和基本见解。该提案的一个关键区别方法是 PI 使用连续近似来分析囊泡群体的进化，而不是专注于分析孤立囊泡的生长。这种方法得益于 PI 实验室的两项关键发现：(1) 发现了一种基于纤维素的形成巨型囊泡的方法，(2) 一种用于大规模分析图像的停止生长方法，可以表征整个群体来自样品的囊泡。 PI 将通过实验、分析和数值建模的结合来实现他的综合研究和教育目标。研究目标包括：（1）通过研究纤维素纸上产生的巨型囊泡的整个群体来了解囊泡的动态。 (2) 通过双层静电力和膜波动力的受控扰动来解读控制囊泡形成的分子间和/或表面间力。 (3) 通过暂时将生长过程与装载货物的过程分离，了解囊泡形成过程中离子溶质的封装过程。教育和推广部分包括：（1）将实验室部分和新课程纳入生物工程课程，旨在培养基于探究的学习模式。 (2) 开发可定制的“SynCell 工具包”，将在 K-12 课堂中实施，以鼓励 K-12 学生从事 STEM 职业。 (3) 为高中生、本科生和研究生提供研究经验的机会。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。