Research: Short Description
updated Oct 2009
Robin Smith is a graduate student with Jerry Feigenson's Membrane Biophysics group at Cornell University. She studies models for the cell membrane using spectroscopy and computation. The cell membrane is a complex mixture of lipids, cholesterol, and proteins. To examine how lipids organize to promote protein function, she focuses on a chemically simplified three-component mixture containing cholesterol plus one lipid with a melting temperature below freezing and a second with a physiological melting temperature around 37 C. These three components give rise to rich phase behavior, including coexistence of ordered and disordered liquid crystalline plus gel phases as a function of temperature and composition. Coexisting ordered and disordered liquid phases form round domains that don't mix, just like oil and water, says Robin. These domains are also believed to exist on a sub-micron scale in the cell membrane. The packing order and diffusion rates exhibited by the lipids in these phases differ. In particular, cholesterol stiffens the membrane to create a liquid-ordered phase believed to be preferred by certain proteins.
To determine whether this heterogeneity is the result of true coexisting phases or mere nonrandom mixing, domain sizes must be measured. Since these domains are smaller than the resolution of light microscopy, their sizes are measured indirectly by analysis of fluorescence resonance energy transfer experiments. Robin also uses electron spin resonance to sense local lipid environment. Monte Carlo simulations of interaction energies between the lipids will provide more information about equilibrium thermodynamics of lipid mixing, perhaps answering why domains do not grow large.
Where are these experiments leading? Ultimately, we want to know how lipids and proteins interact in the cell membrane to carry out vital functions for the cell, says Robin. Determining whether nanoscale domains exist for three-component mixtures of lipids alone is a first step toward examining perturbations introduced by a small transmembrane protein. The interaction between lipids and proteins definitely contributes to heterogeneity in the cell membrane, but to examine the mechanism giving rise to these complex behaviors we must fully understand the interactions between lipids themselves.