Mechanical Effects Of Peripherally Binding Proteins On Membrane Tethers

Our understanding of cell membrane remodeling by proteins has been informed largely by observations of membrane tubulation by proteins in vitro and in vivo. Structural and spectroscopic studies have revealed some important details of the interactions between these proteins and lipids. However, a quantitative description of membrane curvature sensing and generation by proteins, which would guide assessment of the roles of specific proteins and evaluation of hypothesized mechanisms of action, is currently lacking.We are studying membrane curvature sensing and generation by purified proteins using a fluorescence microscopy-based biomimetic curvature gradient manipulation system, the properties of which are described by membrane elasticity theory. Using tethers of controllable curvature pulled from giant vesicles, we monitor protein partitioning between vesicle and tether, and the effects of proteins on tether properties. These measurements direct our assessment and development of statistical mechanical models that clarify the parameters responsible for protein sensing and control of membrane curvature. Our quantitative framework is used with varying membrane composition and solution conditions to reveal subtle differences between various proteins in their membrane restructuring and curvature propensities.