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Часть III
A Pavlov of cell biology
Guenter ALBRECHT-BUEHLER. Ph.D. Robert Laughlin Rea Professor Emeritus, Feinberg School of Medicine Northwestern University.
For me as a freshly baked PhD physicist, who was increasingly fascinated by biophysics, the biology of animal cells seemed particularly attractive. For more than half a century, biology had been dominated by genetics and biochemistry. As a result, the leading biologists of the time focused on molecules, bacteria, and flies, convinced that the answers gleaned from these research targets would uncover all fundamental secrets of life. I was told that Francois Jacob (1920–2013) had famously formulated this belief with the words: «What is true for E. coli, is true for the elephant.»
Being especially fascinated by the strange movements of human and animal cells, I had my doubts. Obviously, the cells in the human body moved in the most complex ways and for the most mysterious reasons. However, they neither used flagella like E. coli, nor did they have little muscles to flex like Drosophila flies. I had learned this from the pioneering work of Michael Abercrombie (1912–1979). He had found that animal cells, while migrating on a flat glass surface, extended and retracted three universal surface extensions.
One class of cellular surface extensions were the so-called «blebs». They were hemispherical «bubbles» that the cells blew up and deflated again. A second kind of extensions, the so-called «filopodia» were long, thin needles that the cells waved around, reminiscent of probing tentacles. Finally, and perhaps most bewilderingly, the cells pushed thin sheets of cytoplasm, called «lamel-lipodia», predominantly in the direction of migration and parallel to the plane substratum on which they migrated. Periodically, however, they folded the lamellipodia back onto their main body, where they fused with it. That was called «ruffling», and it was particularly intriguing, because a cells lamellipodia never fused with the body of another cell that it happened to touch. It was as if the cells had a sense of «self».
Whatever the role of these cytoplasmic projections in the mechanism of locomotion of non-muscle cells, it was clear, that one would not understand them better by studying muscle cells and the molecular interactions between the muscle proteins actin and myosin of the Drosophila fly. After all, when migrating, the non-muscle cells extended their cytoplasm. In contrast, the muscle cells could only contract their bodies. They could not expand them…
This was one of those moments in science, when the method of stretching the established common theories cannot fit the novel data. A breakthrough was needed, which required ignoring the accepted wisdom and starting afresh.
Yuri Vasiliev and his friend and famous mathematician Israel Gelfand did just that. They ignored the widely researched question: «How does the molecular motor of muscle cells deliver the energy required for locomotion?» Instead, they asked the profound and entirely novel question: «What determines inside the amorphous body of a
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