The first morning of BPS 2023 began like a scene straight out of Klara and the Sun (2021), with "the Sun pouring his nourishment" onto the three of us. A moving live music performance and the buzz of early-morning San Diegoan chatter filled the decommissioned photography studio that is now IZOLA bakery on G & 13th. (It opens next on Thursday morning, highly recommend.) In front of me were the most buttery chocolate croissant I have ever had in my life, a strangely delicious oatmilk mocha latte in a can, my two labmates enjoying their equally buttery breakfasts, and the first new friend we made since touching down on the West coast: K, a local musician who generously invited us to share his table (the last seats still available), and who, as it happens, is conducting some audio work at the convention center for our conference. (The conference world is a smaller world than I thought.) This was all certainly different from the breakfasts I am used to, but a refreshing and wonderful (if uncharacteristically early) way to begin the conference experience. At least for Day 1, I happily did as the Romans do.
Walking back toward the convention center, my two juniors stopped for another coffee (I don't know how these kids do it!), and we at last began our weeklong scientific journey. We split up at first, sampling different sessions and scoring some early BPS swag, but eventually we reconvened and collectively migrated to the Mechanobiology symposium at 6E, where, appropriately enough, collective molecular and cellular behaviors were the objects of discourse. As someone who has spent my PhD thinking about autonomously acting single cells (T cells of the mammalian immune system), this was a welcome call to leave my intellectual comfort zone for a moment and start thinking about cooperation and competition in close quarters. The sign of a good session is when there's something fascinating in each talk one has the chance to attend:
Jana Sipkova of the Franze lab in Cambridge opened our proceedings with some beautiful work on how retinal ganglion cells, neurons in the developing frog eye, correctly navigate extremely long processes towards a region of the hindbrain quite distant from themselves -- "like reaching over from San Diego to L.A.," she said for scale. She showed a striking phenotype whereby cell compaction at their destination leads to a collective stiffening that serves as the instructive cue for retinal neurons to feel their way through and connect properly.
Tamal Das from TIFR in Hyderabad then followed up with a couple of vignettes on force balance and imbalance during collective cell behaviors. The first was an epithelial defense system against tumorigenesis, achieved by mechanical extrusion of "bad neighbors" (e.g., Hras mutants) -- interesting to this immunologist because it's done completely in absentia immunitas. The second was a set of beautiful movies showing how sudden spikes in traction forces indicate the designation of leader cells during collective cell migrations. In Rome, the strong lead.
Brian Zhong of the Dunn lab at Stanford regaled us with tales of genetically encoded molecular force sensors. Our lab is definitely going to be interested in some of these constructs! My favorite experiment was one in which a protein donut was fashioned to measure mechanosensitivity: a GAIN domain borrowed from a certain Latrophilin protein was looped onto itself, chemically ligated to the floor on one end, and linked to a tiny magnet on the other. Magnetic tugging was used to measure strain-induced subdomain dissociation.
Min Wu of Yale shared fascinating work on biological oscillations in single cells like starfish oocytes, Dicty, and mast cells. The mixed-mode oscillations they observe are as beautiful as they are complex -- what's really impressive is how the group managed to spectrally decompose the signals, categorize them into high- and low-frequency domains, and even identify genes and pathways to predictably play around with the oscillation patterns. A certain mast cell movie really brought things full circle for me, taking me right back to a Belousov-Zhabotinsky simulation during my undergrad days in the Philippines.
Yee Han Tee from the Bershadsky lab at the MBI-NUS in Singapore proffered a whirligig tour through symmetry breaking events on the cellular scale. Beautiful movies and images showed spontaneous twisting of concentric actin architectures into clockwise and counter-clockwise spirals, as well as the spontaneous tilting of cells grown in microwell chambers. These choices were, interestingly, dependent on the activity of some very familiar actin regulators that we all know and love such as mDia1 and profilin; weirdly, alpha-actinin-1 actually was important for twisting the other way round.
The session's award winner and keynote speaker was Alba Diz-Muñoz from EMBL Heidelberg. After an inspiring summary of her intellectual journey to date, Alba shared a wonderful story on the connection between the cellular plasma membrane and its underlying cytoskeleton. The membrane-cortex attachment is no boring glue; it is actively regulated, and actively regulates, in turn, the mesoscale mechanical fate of cells. By a technical tour de force involving FIB-SEM, cryoelectron tomography, and organelle annotation, she discovered that this anchorage acts less like a boring adhesive and more like a dynamic nanogate that determines the constellation of protein assemblies and resulting architectures within that critical interfacial space.
I unfortunately couldn't attend every talk from the session, but it was a great time thinking in terms of collective behaviors for some hours. I realized that cells, funnily enough, somehow also think to "do as the Romans do" under the watchful eye of the microscopist. But there is another interesting lesson to take home from this session: that the tissue of Rome, as it were, also emerges from a shared history and culture, an intersubjective field -- in other words, from collective experience. For those short hours, we were collectives thinking about collectives.
Now, if there's anything I've learned from [18F]-fluorodeoxyglucose imaging of the brain, it's that maintaining symposium-level mental focus for symposium-length periods of time is bioenergetically costly. And so, after the session, my labmate and I quickly beelined to Tacos El Gordo on F St. & 5th Ave, two blocks away from the historic Balboa Theatre, for an emergency meal. (I actually already had a late-night meal there the night before, but it's always good to reproduce one's most compelling phenotypes, right? Just being a proper scientist here.) The smoke and flashing pans and ingredients flying around were a sight -- and smell! -- to behold, an assault on all the senses even hours before its characteristic evening rush. If the taco restaurant is a kind of collective movement, the taco restaurant's menu is more like a partition function: a beautiful account of microstates, listing all the delicious ways by which humanity has figured out how to deploy toppings onto a double-soft-tortilla-shell (and make it make sense).
Many a food program on Netflix has pontificated on what makes the taco special: the common thread is that it somehow manages to combine a simplicity of essence with vast combinatorial complexity; in other words, it is finitude grazing infinity. It almost reminds the conference attendee of how arrangements of molecular building blocks generate the entire range of macromolecules that constitute us, how our cells can come together in weird and wonderful collectives with their own emergent behaviors, and also how organismal evolution is a constant arrangement and rearrangement of genes, body plans, and natural environments -- except more delicious.
Postscript: What properties might we derive from the taco menu as partition function? Happiness, Satiety, Value-for-money? Maybe the sense that we are more than the sum of our parts. Maybe the compelling feeling that even prior to figuring it all out, we might as well enjoy the emergent.