The Chemical Potential of Membrane Cholesterol Regulates the Metastatic Phenotype in a Cell Culture Model of Breast Cancer
Wednesday, July 22, 2015 - 9:00am - 9:50am
Chemical potential is the standard, quantitative thermodynamic measure of the energy of a molecular species in its actual environment. Despite this and the biological importance of cholesterol, its chemical potential in membranes had never been measured. My laboratory has developed a simple and reliable method to do so. For a variety of cultured cells, including non-metastatic breast cancer cells, the chemical potential of cholesterol (µCH)is maintained at a level of about −2.0 kBT per molecule relative to crystalline cholesterol. But for a metastatic breast cancer cell line, µCH is appreciably greater, at about −0.5 kBT per molecule. In light of these observations we developed a method to alter and maintain µCH in plasma membranes of cultured cells at any desired level. We found that lowering µCH in the metastatic cell line to that of the non-metastatic line significantly reduced the expression levels of several key proteins implicated in breast cancer progression and metastatic spread. Theoretical hypotheses and modeling could greatly facilitate directions for new experiments and for determining mechanisms. As examples: Why might µCH control the state of cancer cells? If µCH is not artificially set, why do the cellular values jump between two discrete ranges that are separated by a large difference? Is the transition between states analogous to a phase transition; if so, can a model be devised that can be experimentally tested?