CAREER: Revealing the fundamental interactions of cell-penetrating nanoparticles in a complex model membrane

University Of Tennessee Knoxville, Knoxville TN

Investigators

Abstract

This CAREER award supports a transformative research and education program to understand how novel types of nano-scale particles penetrate cellular membranes in a passive and seemingly nondestructive manner. Revealing these details will unlock tremendous potential for developing useful cell penetrating agents in biomedicine and agriculture and enable us to better discern the safety of nanomaterials. To lay a foundation for lasting scientific contributions, the research project will leverage new methods pioneered by the Principal Investigator to assemble and characterize complex model membranes that better mimic those found in cells. This research will generate new knowledge of how the chemistry and patterning of nanoparticle surfaces enable their uptake in cells, which will directly benefit the design, testing, and use of new generations of nanomaterials. Closely tied to the research project, an educational and outreach program entitled INTERFACE will enable a wider range of people to engage in and interact with the research and technologies produced in the PI's lab as a result of this project. INTERFACE includes public forums on the nature and context of bio-active nanoparticles, hands-on research activities for K-12 and undergraduate students, and support for STEM-focused journalism and improved science communication activities. These activities support broader impacts by generating interest in STEM, educating the public, improving scientific journalism, increasing participation of underrepresented groups, and enriching engineering curricula. This CAREER award supports a transformative research and education program to understand how novel types of amphiphilic monolayer-protected nanoparticles passively, and seemingly nondestructively, penetrate cellular membranes. Revealing these mechanisms will unlock tremendous potential for cell penetrating agents in biomedicine and enable us to better discern the safety of nanomaterials. To lay a foundation for lasting contributions, the proposed project will leverage new methods pioneered by the PI to assemble complex lipid bilayers that better mimic membranes in cells and characterize in situ both their structural and transport properties. The research project seeks to: 1) develop transformative tools for manipulating, characterizing, and imaging complex model membranes; 2) quantify the effects of amphiphilic nanoparticle adsorption, insertion, and translocation on membrane structure; 3) uncover the effects of lipid type and thermotropic phase on nanoparticle activity; and 4) examine converse effects of nanoparticles on lateral organization in membranes. The intellectual merit stems from the stated objectives and expected outcomes to clearly understand how amphiphilic nanoparticles penetrate membranes by linking their activities to membrane capacitance, thickness, tension, intra-membrane potential, conductance, and lateral organization of peptides. By studying homogeneous and heterogeneous membranes that can be assembled to mimic a variety of cells, this work will generate new information about which lipid domains are preferred and test hypotheses that amphiphilic nanoparticles prefer defects, areas of higher curvature, and cholesterol-lean regions. Closely tied to the research, an educational and outreach program entitled INTERFACE will enable a wider range of people to engage in and interact with the research and technologies produced in the Principal Investigator's lab as a result of this project. INTERFACE includes public forums on the nature and context of bioactive nanoparticles, hands-on research activities for K-12 and undergraduate students, and support for STEM-focused journalism and improved science communication activities. 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.