Topic Overview:
Dr. Spence’s laboratory is developing new magnetic resonance-based imaging techniques to directly observe lipid domains in the cellular membrane.  Lipid domains are hypothesized to play an important role in the organization of membrane proteins, actively orchestrating protein-protein interactions by sequestering particular membrane proteins while shunning others.  Medical research shows an important role for lipid rafts in the progression of Alzheimer’s disease and in HIV infection.  Although an abundance of indirect evidence supports the importance of lipid domains in biological systems, lipid domains in cells have proven too small for optical detection with fluorescence microscopy. New imaging techniques are critical to understanding the active role that lipid domains might play in biology and medicine.
Dr. Spence combines magnetic-resonance imaging (MRI) techniques with solid-state nuclear magnetic resonance (NMR) to measure the diffusion of lipids within the membrane.  When domains are present, a marked slowing is observed in the apparent diffusion rate of the lipids confined within the domains.  By measuring the time-dependence of diffusion, domain sizes as small as 100 nm, well below the ~300 nm diffraction limit of optical microscopy, can theoretically be measured.  Dr. Spence takes advantage of the noninvasive nature of magnetic resonance to measure diffusion in intact membranes.  In addition, by detecting the protons present on the native lipids themselves, it is not necessary to use molecular labels like fluorescent dyes. 

Structural models for cellular lipid domains are based on domains observed in model membranes (purified lipid mixtures). Although micron-scale lipid domains in model membranes are easily observed with optical microscopy, as noted earlier, lipid domains in cells are thought to be too small for optical resolution (~10-200 nm.)  This discrepancy between model and cellular membranes is an open mystery.  Dr. Spence employs her imaging techniques to examine the structural differences between model and cellular membranes and how these differences (curvature, membrane proteins, cytoskeleton) affect the formation and sizes of domains.  She has shown that introducing perforations to a model membrane modulates the formation of lipid domains―a novel demonstration of how membrane morphology can change the phase behavior of domains.