In order to obtain further insight into the molecular mechanisms governing biological membrane organization, we use a combined approach of atomic force microscopy (AFM) and single molecule fluorescence. The former technique can be applied to characterize the mesoscopic structure of both model and native membranes. On the other hand, highly sensitive fluorescence measurements, like Fluorescence correlation spectroscopy (FCS), 2-Focus Scanning FCS or Total Internal Reflection Fluorescence (TIRF), can be employed to obtain information about dynamics in complex lipid systems.

We exploit these different approaches, at the very same time and within a single experimental apparatus, to study supported bilayers of biological relevance, determining the lateral organization of lipids and membrane proteins therein. Topographical data provided by the nanoscopic spatial resolution of the AFM, are immediately supported by laser scanning imaging, and then joined in real time with the dynamics information deriving from FCS.

This effective combination could help to shed light on the physiological role of lipidic microdomains and, more in general, on lipid-lipid and lipid-protein interactions, ruling out possible imprecisions or artefacts coming from the use of a single technique.

Selected Publications

Zhao X, Weisleder N, Han X, Pan Z, Parness J, Brotto M, Ma J. Azumolene inhibits a component of store-operated calcium entry that is coupled to the skeletal muscle ryanodine receptor. 2006; J Biol Chem. 2006; 281(44): 33477-86.

Weisleder N., Brotto M., Komazaki, S., Pan, Z., Nosek, T., Parness, J., Takeshima H, and Ma J. Muscle aging is associated with compromised Ca2+ spark signaling and segregated intracellular Ca2+ release. J. Cell Biol. 2006; 174(5): 639-45. Comment in: J Cell Biol. 2006 Aug 28;174(5):613-4.

Cai C, Lin P, Cheung KH, Li N, Levchook C, Pan Z, Ferrante C, Boulianne GL, Foskett JK, Danielpour D, Ma J. The presenilin-2 loop peptide perturbs intracellular Ca2+ homeostasis and accelerates apoptosis. J Biol Chem. 2006; 281(24): 16649-55.