Before the Banquet

After a meal of local delights, everyone heads back to more exciting science.

Yusuke Toyama started the session by telling us about how forces in the system when apoptotic cells extrude out from the epithelial monolayer. Drosophila epithelium was used as the model system. This is a complex process where the cells cant leave a hole in the monolayer. To prevent formation of this hole, there is a complex gymnastic of forces and remodeling of cell-cell junctions. He showed that at early time points when perhaps apoptotic cells decide to leave, the tension at the junctions is relaxed, this is followed by an increase in tension to restore it to normal levels at the junctions once the cells have been extruded. What a beautiful intricate mechanism to ensure that no holes are left and the monolayer is not weak at any point in space. These force changes were also observed in monolayers on a dish using traction force microscopy.

Switching gears, Marvin Whitely told us about building houses for bacteria. This is an amazing technology where they can use a few bacteria to colonize a pico liter home made of PDMS, and this is used to study the social lives of bacteria. One of the most important questions is the simultaneous existence of Pseudomonas and Staphylococcus in chronic infections or cystic fibrosis in humans. These are drug resistant and are a simply a real pain! They show that these bugs coexist in separate clusters and don’t intermix. These clusters are 4-13um apart, suggesting that they are not randomly positioned. Guess what causes proper positioning? One bacteria produces food (lactate) for the other but (perhaps to protect its space) it also produces a toxin (H2O2) for the other. They further show that in bacterium 2, the gene for dispersal is under the promoter that responds to peroxidase levels. At high peroxidase levels these bacteria disperse. Bacterium 1 is a great neighbor to provide food at the same time ensuring that the neighbors don’t get too close. If only humans could have such beautiful designs in society, imagine not crowded cities but everyone had food to eat.

Then we switched back to forces experienced by integrins, a topic close to my integrins. Alex Dunn from Stanford University, has developed (in his lab) and used (from other labs) beautiful FRET based sensors to generate force maps in the whole focal adhesions. These sensors are elastic springs that are tagged with a fluorophore at either end. They are attached to glass at one end and present the ligand at the other end. This was done at a single molecule precision using a few fluorescently labeled FRET probes whereas in a sea of unlabeled probes. Using this, they find that most integrins bear low force (if about 3pN) whereas a few integrins bear higher forces (in the range of 7pN). Alex gave a fantastic analogy of feet of a starfish that stick because of very many feet exerting very low forces. Now one can begin creating physical models of how focal adhesions are formed and maintained. This also helps the cells to provide a buffer wherein they can bear forces 10X(safety factor) higher than what they normally exert, and hence provides robustness in the system over a large dynamic range.

With that we had Pere Roca-Cusachs, tell us about integrins exerting forces on soft versus rigid substrates. In collaboration with Ada Cavalcanti, they use gold nano dots to present integrin ligands (RGD) to the cells. This was done on both soft and rigid substrates. Surprisingly, they find that cells can spread more easily on soft substrates with fewer ligands i.e if the ligands are more separated (~100nm) on the soft substrates, cells can still spread whereas on rigid substrates they spread only when the ligands are spaced not more than 60nm apart. This suggests a different mechanism of clutch engagement, wherein with low forces the adhesion can grow larger. They further test this by adding Blebbistatin (to inhibit myosin and lower forces) and observe that the adhesions grow in size.

Final talk of the session was by Priyamvada Chug from Ewa Paluch’s lab @ UCL. During her PhD, she studied the role of cortical thickness in exerting force, as the cells undergo cytokinesis during mitosis. They developed careful tools to measure cortical thickness and performed an RNAi screen to identify modulators of cortical thickness. The major players they isolated regulated the length of actin fibers. This was not regulated by Myosin II contractility only. Factors that shorten (e.g Capping proteins) or increase the length of actin fibers (Diaphanous) increase the cortical thickness. This was indeed a very interesting demonstration of non-monotonic dependence of cortical thickness on an optimal length of actin fibers

That led us into the last poster session. The posters were amazing ranging from engineering approaches to modulate the matrix to genomics approaches to understand regulation of various cancers. Beautiful imaging to answer such important questions was of course my favorite. I am definitely registering for the 2017 BPS annual meeting, where Eric Bretzig will deliver the national lecture.

This was followed by the conference banquet. An amazing venue – Singapore Yacht Club, overlooking the bay as the sunset. It was surprisingly not too humid and the cool breeze made the weather just perfect. I enjoyed discussing  lamin A/C, another mechanoregulated skeletal element I’m interested in, with fellow attendees. This was followed by interesting an interesting discussion about the U.S. Presidential election! I would safely say that this has been the most entertaining presidential race that I have witnessed and of course I look forward to more drama.

Some of us headed out to the city to enjoy more drinks and discuss science in the backdrop of the city center. The city does look colorful at night!

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