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.

非技术摘要这一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状囊泡的组装。大自然使用膜封装生物细胞。了解自然界中的过程，然后构建模仿细胞膜的囊泡是有用的。例如，可以将囊泡用作微观化学反应堆，也可以用作封装和可控释放治疗药物的车辆。主要研究者（PI）和他的学生将研究物理参数的影响，例如温度，溶液的离子强度以及磷脂的电荷密度对囊泡形成。研究小组将在不同的身体条件下研究离子货物囊中囊泡的囊泡。收集的实验数据将用于构建和测试分析和数值模型，以更好地了解囊泡形成的过程以及封装货物的过程。该奖项还将支持PI通过设计新的动手实验室课程来增强本科和研究生生物工程课程的努力。 PI将创建一个可自定义的实验工具包“ Syncell Toolkit”，该工具包将在K-12教室中实施，以增加对生物材料研究的兴趣。该奖项将为高中，本科生和研究生在相对服务不足的加利福尼亚州中部地区的多元学科环境中为研究经验提供机会。技术摘要：巨型囊泡是模仿生物学细胞最小构型的体外结构。仍然缺乏对囊泡过程的一般理解，这导致表面支持的近核磷脂膜形成巨大的囊泡。该职业奖将支持一项综合的研究，教育和外展计划，以获取对巨型囊泡形成的基本过程以及囊泡中溶质的封装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种群的演变，而不是专注于分析分离的囊泡的生长。 PI的实验室中的两个关键发现启用了这种方法：（1）发现基于纤维素的方法来形成巨型囊泡，（2）一种停止增长的方法，用于大规模分析图像，这些方法可以从样品中表征整个囊泡的整个囊泡。 PI将通过结合实验以及分析和数值建模来实现其综合研究和教育目标。研究目的包括：（1）通过研究在纤维素纸上产生的巨型囊泡的整个种群来了解囊泡的动力学。（2）通过控制双层静电力和膜起伏力来控制囊泡的分子间和/或表面上的力。（3）通过将生长过程与装载货物的过程脱钩，了解囊泡过程中离子溶质的封装过程。教育和外展组成部分包括：（1）合并实验室组件和新课程，旨在促进生物工程课程的基于询问的学习方式。（2）开发可自定义的“ Syncell工具包”，该工具包将在K-12教室中实施，以鼓励K-12学生从事STEM的职业。（3）为高中，本科生和研究生提供了研究经验的机会。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响评估标准，被认为值得通过评估来获得支持。