The wall celebrating veatchlab alums is up just in time for the start of the academic year at @UMBiophys including a few new ones representing @ss_shelbs , @suminkim28, and Thomas Shaw. Your impact looms large.

(figure 1 in in doi.org/10.1016/j.bpj.2023.0…)

Introducing Dr. Thomas Shaw! Congrats to Thomas for a great talk and thesis -- and check out that cake made by veatchlab members and alums including @ss_shelbs @AdamDecker98 @JenChemFlan inspired by a figure made by @biophysnerd!

Takeaway: we think that these domains at BCR clusters have tunable contrast because they integrate both the stimulus (related to proteins brought to the domain through protein interactions) and the membrane thermodynamics (how close the membrane is to its phase transition).

Not only did this manipulate how anchors sort w/r/t BCR clusters, it also tuned the magnitude of BCR Tyr phosphorylation! This nicely corroborates existing work implicating lipid rafts in BCR activation, now w/ a direct connection to the underlying membrane phase transition.

We tuned contrast two ways: first by co-clustering BCR with minimal “co-receptors” to alter the stimulus, and second by adding hydrophobic small molecules to manipulate membrane thermodynamics by shifting the phase transition temperature.

Now for that twist: we noticed that these domains at BCR clusters sort anchors less strongly than phases in vesicles. In other words, domains in cells have lower “contrast” than ordered domains in phase separated vesicles. Maybe contrast can be tuned?

We can also look at anchor dynamics, and anchor confinement near BCR clusters is also strongly correlated with partitioning in vesicles. Conclusion: the membrane phase transition drives both the concentration and retention of membrane components within domains.

They agree very well! Anchor partitioning between vesicle phases quantitatively predicts anchor concentration near BCR clusters. Conclusion: membrane phase separation is a physical driver of domain formation around clustered BCRs.

At the same time, our awesome collaborators in @leventallab measured partitioning of the same anchors in phase-separated giant plasma membrane vesicles (GPMVs). Both measurements basically quantify local concentration of anchors, so we can compare them directly. When we do…