CAREER: Biological tuning of plasma membrane mixing

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

All animal cells are surrounded by a plasma membrane that defines the outer surface of the cell. Cells control the protein and lipid composition of their plasma membrane to support a broad range of functions, including acting as a sensor of the local cellular environment. For example, the plasma membrane senses and communicates to the cell interior when it is appropriate to grow and divide, if and where the cell should crawl, or when certain compounds or classes of compounds are present in the vicinity. This project will investigate how and why cells adapt their plasma membrane composition in response to several changes in their growth conditions. Many of these sensing functions are thought to depend on how proteins and lipids are organized within the plasma membrane, and the researchers will investigate how both membrane heterogeneity and sensing functions are impacted as cells adjust membrane composition. The long term goals of the project are to discover how cells maintain a heterogeneous membrane, and how this membrane structure contributes to the efficient functioning of the cell. The researchers will communicate their findings through publications, conference presentations, public lectures, development of undergraduate curricula, and outreach to high school students from backgrounds that are under-represented in the physical sciences. The principle investigator will train undergraduate and graduate students for careers in STEM fields. Plasma membranes isolated from intact cells separate into two liquid phases when cooled below room temperature, similar to oil and water in three dimensions. The presence of this phase transition at low temperature predicts the existence of smaller membrane domains at the higher temperatures where cells live in culture. The objective of the research is to directly observe domains in intact cells at growth temperature, and to determine if cells tune their membrane composition to control the physical properties of these domains in order to optimize cellular functions. The research will use conventional cell biological, biochemical, and biophysical techniques as well as cutting edge experimental methods, including super-resolution fluorescence localization microscopy to image the nano-scale organization of membrane components and quantitative lipidomics to detail plasma membrane lipid composition.