Dynamics of the Living Cell – Consequences of Inoué’s Research

Shinya Inoué’s new methods of visualizing healthy living cells has contributed to a dynamic picture of the cell. In recognition of his research, he has been awarded prestigious prizes such as the E. B. Wilson Medal from the American Society of Cell Biologists, the Ernst Abbe Memorial Award from the New York Microscopical Society, and the International Prize for Biology from the Japan Society for the Promotion of Science. His work on the mitotic spindle demonstrated that the spindle itself is in dynamic equilibrium.

Inoué proposed that the spindles were polymers, and that when they depolymerize, as they did when he applied colchicine to the cell, they move the chromosomes to which they are attached. Biologists now know that the spindle fibers are microtubules, polymers made from two versions of the molecule tubulin, known as alpha-tubulin and beta-tubulin. One alpha-tubulin molecule and one beta-tubulin molecule bind to form what is known as a ‘tubulin heterodimer’. Tubulin heterodimers line up to form what are called ‘protofilaments’, which assemble lengthways, side-by-side with each other. This collection of associated protofilaments is a microtubule. The ends of the microtubule are typically depicted like the frayed ends of a rope. This is because at those ends, tubulin heterodimers are constantly in the process of being added (polymerization) and removed (depolymerisation).

There is not a static state, but the microtubule is constantly subjected to depolymerisation and repolymerization. It is in a state of dynamic equilibrium, or dynamic instability. Even if the microtubule appears not be changing, for example staying the same length, this is only because the processes of depolymerisation and polymerization cancel each other out. Depending on the conditions, such as the presence or absence of chemicals like colchicine, one process may proceed more quickly than the other.

In an era when versions of electron microscopy has captured the imagination of the public and the attention of scientists, Shinya dedicated his long research career to finding new ways to improve the capabilities of optical or light microscopy. He did this because only optical microscopy is able to view the dynamic processes in living cells that occur in real time. The observer has to interpret what he or she sees, but they do not have to work out how the static images of fixed samples that they see relate to the processes they think might be happening. Shinya continuously found ways to improve his ‘Shinya-scopes’, and incorporate new technologies to increase their power, to allow scientists to visualize the inner cell.

From his initial polarizing optical microscopes, through his development of super-resolution video microscopy, to joining approaches to enhance the ability to detect the expression of GFP, Shinya Inoué has been at the forefront of the endeavour to understand the strange and seemingly counter-intuitive world of the living cell. He has worked with many dramatically different organisms, across the Tree of Life. He bases this approach on the belief that “unusual organisms tend to provide extraordinary gifts of Nature.” Even into his 90s, Shinya retains his enthusiasm for the opportunities that polarizing optical microscopes offer researchers, and continues to help colleagues develop the technology and techniques still further.