Katsumi Matsuzaki grew up in Osaka, Japan. His father worked for an appliances manufacturer and his mother for Nippon Telegraph and Telephone. As a young person, he was interested in a career as a medical doctor, and became interested in chemistry once he had been exposed to the subject in school. When he began his undergraduate career at Kyoto University, he decided to study in the pharmaceutical sciences department: “something between medical science and chemistry,” he says. “When I was a fourth-year student at Kyoto University, I joined Professor Masayuki Nakagaki’s lab, in which people investigated colloid and surface chemistry. The project I was involved in was a very basic one on interaction between fluorescent dyes and micelles or liposomes. I studied spectroscopy and membranes.” From then on, Matsuzaki has worked primarily on membrane biophysics, except during his time working for a pharmaceutical company.
Matsuzaki received his Bachelor of Science degree in biophysical chemistry in 1982 and remained at Kyoto University to pursue his master of science degree in biophysical chemistry in Nakagaki’s lab. After this, he worked at Takeda Chemical Industries Company for several years before returning to Kyoto University in 1987 as an assistant professor and began work on his PhD. “Luckily the antimicrobial peptide magainin was discovered in that year,” he says. “So, I decided to study interaction of this peptide with membranes, because it was suggested to perturb bacterial membranes.”
He earned his PhD in biophysical chemistry in 1992 for his thesis “Physicochemical Studies on Interactions of Antimicrobial Peptides, Hypelcin A, Trichopolyn I, and Magainins, with Lipid Bilayers.” He stayed at the Biocenter of the University of Basel, Switzerland, for ten months as a visiting scientist in 1993, working with Joachim Seelig.
When he began working on magainins, Matsuzaki says, “few scientists were (and still are) interested in peptide-lipid interaction in Japan. Therefore, it was difficult to get grants.” He was able to find funding by applying for as many grants as he could, and remained at Kyoto University. He became an associate professor in 1997 and then a full professor in 2003, the position he holds today.
Matsuzaki’s lab works on several projects. “We have investigated interaction of antimicrobial peptides with membranes for almost 30 years and proposed the concept of ‘torpidal pore’ for the first time in 1996,” he explains. “My current interest is their interaction with human cells and how to improve the therapeutic index for future clinical application.” The lab is also studying the mechanism of amyloidβ-protein on membranes. “We have struggled with this project for more than 15 years, and found that clusters of gangliosides on neuronal cells facilitate the formation of ‘toxic amyloids,’ in contrast to ‘less toxic’ amyloids formed in aqueous solution,” he says. “An ongoing project is to solve the structure of this unique amyloid and to elucidate the molecular mechanism of its formation.”
Matsuzaki’s lab also works on thermodynamics of interaction between transmembrane helices. “Our 15-year work elucidated that a basic driving force of association of transmembrane helices is interaction between helical macrodipoles, which is significantly modulated by surrounding lipids,” he explains. “Recently, we succeeded in real-time monitoring of association-dissociation dynamics using a single-molecule FRET technique.” The lab also studies interaction between membrane proteins in living cells “We developed a coiled-coli tag-probe labeling method in 2008. This method combined with a spectral imaging technique enabled stoichiometric analysis of oligomerization of membrane proteins on living cells,” Matsuzaki says.
His favorite aspect of biophysics, he notes, is that “in contrast to cell biology and biochemistry, biophysics can monitor biological phenomena in real time and in a non-disruptive fashion. Biophysics also tells us their driving forces.” Going forward in his career, he hopes to monitor conformational chances of membrane proteins in living cells in real time, with minimal perturbation.
Matsuzaki’s friend and colleague Ayyalusamy Ramamoorthy, University of Michigan, recalls meeting him at a Biophysical Society Annual Meeting. “He was one of the speakers of a special session on antimicrobial peptides. Graduate students from my laboratory and myself were in the audience, as we were investigating the high-resolution structure and mechanism of action of several different antimicrobial peptides” he says. “His inspiring talk further motivated us to dedicate ourselves to research in this area. He also showed great enthusiasm for our research and he came to our posters to talk with my research group. […] Katsumi is a brilliant and honest scientist. He thinks about a chosen research problem very deeply and goes about completing the investigation thoroughly. He is also very kind and an extremely nice person.”
Richard Epand, McMaster University, Canada, also met Matsuzaki at a Biophysical Society Annual Meeting, and the pair went on to collaborate. “We have two joint publications on the role of membrane curvature in pore formation by antimicrobial peptides,” Epand says. “However, our scientific interactions were greater than this, and we exchanged ideas about scientific matters on many occasions. […] There were many useful exchanges that we had that advanced my thinking about scientific problems. During a visit to Kyoto. I saw the book Microbial Lipids by [Colin Ratledge and S.G.] Wilkinson in Matsuzaki’s office. It contributed to my appreciation of the diverse lipid composition of different microorganisms.”
Epand recalls, “He is a loyal friend and is a generous person. Matsuzaki was a hospitable and helpful host on our visits to Japan. […] Against our better judgment, my wife, Raquel, and I joined Katsumi for dinner and had some fugu (blowfish). We all survived, thanks to the chef’s careful removal of all the neurotoxins.”
Matsuzaki himself enjoys traveling, and has another, more unusual hobby. “I collect model trains in various scales from various countries: Japan, Switzerland, United States, and Canada,” he says. “I have built a couple of layouts of the Swiss prototype.” One of his model trains is pictured above.
Matsuzaki would advise biophysicists who are starting out in their careers to, “keep in mind that molecular interactions in membranes are dynamic and change with time,” he says. “Therefore, it is difficult to understand their nature only from ‘snap shot’ results.” He considers this one of the most challenging parts of working as a biophysicist. Matsuzaki also reminds early career scientists, “Discard all prejudices. Look at your data carefully with profound knowledge of biophysics. Then let the data tell their own story. If lucky, you will discover a novel mechanism!”