CAREER: The nanoscale dynamics of molecular sorting, membrane curvature, and endocytosis

Wayne State University, Detroit MI

Investigators

Abstract

Nontechnical: This CAREER award by the Biomaterials program in the Division of Materials Research to Wayne State University is to support the research and educational efforts focused on nanoscale membrane processes. Biological membranes are complex and dynamic two-dimensional fluid structures that are responsible for binding, internalizing and transporting materials. Membrane processes are inadequately understood at present, and this lack of in depth knowledge is limiting biomedical advancement in diverse neurological, immunological, and metabolic conditions. Developing an understanding and resolving the underlying membrane processes would guide the development of novel membrane like materials for potential applications in battery, long term food preservation, liposome-based cargo (drug, DNA, RNA, etc.) delivery without endosome uptake among others. Further, the educational impact of this award will be in the training of a technically skilled workforce, and these efforts will be coordinated with the Michigan Science Center. This award will support the development and implementation of a hands-on educational program to address the Next-Generation Science Standards, and these activities are expected to impact a large number of local K-12 students annually. Technical: This CAREER award supports the development and use of nanoscopic optical methods to measure the molecular-scale causes and effects of membrane curvature and functions. Using polarized localization microscopy, a super-resolution optical technique developed by the PI that is capable of simultaneously measuring dynamic membrane curvature and molecular organization, the following studies will be carried out to: 1) quantify the interplay of nanoscale membrane curvature with lipid phase separation; 2) resolve the contributions of curvature sensing and lipid phase preference on the sorting of phosphoinositide phosphates; and 3) observe the nanoscale membrane organization surrounding clathrin- and caveolin-independent endocytosis. Membrane functions require an understanding of many components of membranes including lateral composition variation, local variations in membrane physical properties such as thickness, bending, rigidity, tension, curvature, and fluidity. By understanding the interdependence of fundamental physical principles that regulate membrane functions, this project would create a foundational understanding in developing novel biomimetic membranes and applications in scientific and technological fields. This research will also address previously untestable hypotheses regarding the mechanisms initiating receptor-independent endocytosis. The results from these studies will guide both basic scientists to understand mechanisms in nano-biology, and applied scientists aiming to better control membrane processes and functions including the interplay between membrane properties that are critical for high-throughput membranes, liposome-based drug targeting, and nanoliter chemistry applications. Additionally, this award will support the development of nanoscopic methods, improved understandings of nanoscale biology, and dissemination of these advancements through the training of students. The proposed educational and training activities in coordination with the Michigan Science Center are expected to impact a large number of K-12 students in preparing them for higher education in STEM and a technically skilled workforce. The economy and society will benefit from the proposed training of a high-tech workforce, improved scientific literacy, new biological insights, and technological advances made possible by this award.