A student research project from the 2016 MBL Physiology course is now published in Biology of the Cell! Below this tweet, course faculty member Manuel Théry from the Hôpital Saint-Louis in Paris describes the excitement of gathering the imaging data — including late nights in Loeb and morning “crisis meetings” — and the surprising result.
3 month after being posted on @biorxivpreprint https://t.co/6rhInR2iMA
the @MBLScience Woods Hole 2016 summer paper about the rise and fall of traction forces during cell cycle progression is out in @BiolCell https://t.co/hACZVT7csG pic.twitter.com/qO5zr7zdtS
— THERY Manuel (@ManuelTHERY) February 2, 2018
By Manuel Théry
During my two-week faculty rotation in the MBL Physiology course, we undertook a very focused research project with the students. Dozens of research papers show how mechanical forces impact a cell’s progression through the cell cycle, as it divides into two new daughter cells. But no papers address the inverse question. Could it be that cells don’t produce the same amount of traction forces depending on where they are in their cycle?
To address this point, we argued that we needed to do two things: measure the force and measure the cell-cycle position. And actually there are two cool techniques to do this, both of which allow you to measure forces and cell cycle by taking a picture! We argued that the truth may get blurred in the dispersion of data due to variations of cell shape and cell movements, so we had to normalize this.
We rented some equipment, we borrowed some cells from colleagues in Boston and … it did not work, of course. But impossible is not Woods Hole, so we had a morning crisis meeting, every morning. We split the tasks. We listed all problems from the day before. We defined new working pairs or trios to solve specific issues. Then we had a crisis meeting in the afternoon. We listed all success and failures. And started again. We worked until midnight but most often until 2 or 3 AM, with our spirits remaining high.
After 10 days of struggle we solved all issues and we could take a picture! One measure! The party was on. But we had only 4 days left before we needed to present our data to the class. We teamed up: Some of us were in charge of the glass coating, others of the micropatterning, others of the gel preparation, and others of cell maintenance. At the end of the day we booked ALL the [traction-force] microscopes for the night and took pictures all night long. (I think once someone unplugged the microscope instead of his laptop … we lost 200 measurements! But we started again at 9 the next morning.)
I had to leave before the last day and go back to France. The teaching assistants, Benoit Vianay and and Fabrice Senger, stayed with the students. They were now working on data analysis to turn the pictures into force measurements. They had only 12 hours left!
I attended the presentation to the class on Skype. The students were really proud to show the data. And they found that from early G1 to late G1 and at the beginning of S phase, traction forces rise. It was kind of expected — cells grow, accumulate material, express more and more proteins and so become “stronger.” But the surprise was that from S to G2 force fell completely back to ground level!
Nobody could have predicted this — well, nobody excepted Physiology course co-director Jennifer Lippincott-Schwarz, from the National Institutes of Health. After our first week of struggle with the experiment, we thought we may fail. So we asked the course directors what they would predict about force variations during cell-cycle progression. Wallace Marshall from University of California, San Francisco, knew the forces would change, but he couldn’t say how. He also thought someone should bet that they wouldn’t change! So he took on that role. Unfortunately, course co-director Rob Phillips of Caltech was not there for the debate. Alex Mogilner, who was visiting the course from Boston University, thought forces would rise linearly until mitosis, then suddenly drop off. And Jennifer said, “Forces will rise until S phase and then fall.” We were all surprised. It made no sense to any of us. … But she was right!
I don’t know about the students but for me, this was the best scientific experience I have ever had. The Physiology course students who contributed to the paper were Simon Alamos, Maya Anjur-Dietrich, Elizabeth Bearce, Bevan Cheeseman, and Lisa Lee.