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

University Of California - Merced, Merced CA

Investigators

Abstract

Non-technical Summary This 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.