Membrane Cooperativity Unit (Akihiro Kusumi)
Welcome to the web page of the Membrane Cooperativity Unit, led by Prof. Aki Kusumi.
We at the Membrane Cooperativity Unit strive to understand how biological membranes work at very fundamental levels by using unique approaches; observing and manipulating each individual single molecule in living cells at a time resolution of 20 µs (1,650x faster than normal video rate). We focus on the plasma membrane among various cellular membranes. The plasma membrane is the outermost cellular membrane which encloses the entire cell. It is critically important for the cell - the fundamental unit of life - because it defines the space for it. The plasma membrane exchanges information, energy, and substances with the outside world, but more interestingly, it functions as a computer to regulate these exchanges, a function generally called “signal transduction.” Our laboratory is dedicated to (1) developing unique methodologies of single-molecule observation-manipulation in living cells (Fig. 1), and (2) elucidating the mechanisms for plasma membrane organization and function, with particular emphases on signal transduction and neuronal network formation, by extensively using single-molecule technologies (Fig. 2).
The plasma membranes of all cells existing on earth have the common structure of a "two-dimensional liquid" (see Fig. 3-(1)). Such universality is comparable to that of the double helical structure of DNA. Like many DNA functions are based on its double helical structure, various plasma membrane functions are enabled by the fluid structure of the plasma membrane. This raises the possibility that we can identify the set of physical properties of the plasma membrane, like those of DNA, that make the plasma membrane work.
Such fundamental mechanisms are likely to be those utilizing the low (two)-dimensionality and modifying the mobility, local concentration, and assembly-dissociation of molecules in-on the plasma membrane. As one of such mechanisms, and perhaps one of the most important mechanisms, we identified the partitioning of the plasma membrane by the meshwork of actin filaments, called actin membrane skeleton (Fig. 3-(2)). In our continued efforts, we found many examples where cooperative assembly of molecules, rather than simple interaction of two molecules, is responsible for key steps in signal transduction and neuronal network formation. Thus, our unit is called “Membrane Cooperativity Unit.” A critically important point here is that many such functional assemblies were transient ones with lifetimes of the orders of submilliseconds to seconds, i.e., they disintegrated right after they formed (and worked), suggesting that the delicate balance between weak cooperativity and thermal fluctuation is important for biological functions (Fig. 4). We now envisage five more cooperative processes are of fundamental importance for the organization and function of the plasma membrane (Fig. 2 (3)~(7)). In particular, we are now trying to understand the three-tiered meso-scale (2~300 nm) domain architecture of the plasma membrane (Fig. 5), which, I think, provides an excellent perspective on the mechanisms of various functions of the plasma membrane.
Details of our earlier work can be found at http://www.nanobio.frontier.kyoto-u.ac.jp/index.html.
Recruiting Students and Postdocs
Students interested in studying for a PhD with us, please contact us for informal discussions about the entry requirements. OIST’s graduate program provides full funding for 5 years and conference travel costs. OIST also offers a research intern program for BSc or MSc students - details are available at https://groups.oist.jp/grad/research-interns . Please email Prof. Aki Kusumi (akihiro.kusumi at oist.jp) to discuss opportunities.