Single Molecules

We use novel optical microscope techniques combined with sophisticated data analysis to reveal dynamics of biological membranes at the nanoscale
Cell membranes are consisted of various types of lipids and proteins. Almost all membrane functions are accomplished by these molecules. A healthy cell could allocate these molecules at the right position at the appropriate time, letting them react. How does a cell mange to do that? Experimental evidence indicate that the cytoskeleton underneath the plasma membrane influences the dynamics of membrane molecules and thus regulates the spatial distribution of membrane molecule indirectly. Moreover, because the membrane composition is very complex, it is also believed that membrane is heterogeneous at various length scales and timescales -- domains can form through the interaction between molecules. These domains could potentially serve as a platform for local concentration and activation of membrane proteins. The aforementioned regulation mechanisms are very delicate; stronger or weaker interactions could destroy the membrane structures and the membrane functions, leading to various kinds of diseases. 

Although many important membrane functions are known with great details, the general regulation mechanisms at the molecular scale remains elusive. The cell membrane is fluidic at the physiological temperature. Membrane molecules diffuse in the two-dimensional membrane driven by thermal fluctuation. A molecule readily diffuses by a few nanometers within just a microsecond. Therefore, to investigate dynamics and regulation mechanisms with molecular resolution, a fast and precise measurement is needed. Unfortunately, it is technically difficult to have both speed and precision in a measurement simultaneously. 

We use advanced ultrahigh-speed optical microscope techniques to study dynamics and regulation mechanisms of biomembranes at single-molecule level. We attach small gold nanoparticles to specific membrane molecules and track their motion in the membrane. The high sensitivity of our optical system allows us to use smaller gold nanoparticles and to track their motion with a higher precision at a higher speed. We are to elucidate the existence of membrane nanodomains and their possible roles in membrane functions.

Selected publications:
“Heterogeneous nanoscopic lipid diffusion in the live cell membrane and its dependency on cholesterol,” Biophysical Journal, 121(16), 3146-3161 (2022).
“Monovalent and oriented labeling of gold nanoprobes for the high-resolution tracking of a single membrane molecule,” ACS Nano, 13(10), 10918-10928 (2019).
“From dynamics to membrane organization: Experimental breakthroughs occasion a "modeling manifesto",” Biophysical Journal, 115, pp. 595-604 (2018).
“Nanoscopic substructures of raft-mimetic liquid-ordered membrane domains revealed by high-speed single-particle tracking,” Scientific Reports 6:20542 (2016).