(1/n) What is common between Silk Road, Klein bottle and a human parasite? Continuing series on extreme biological physics - thrilled to share latest preprint on "Extreme cellular hydraulics” - fantastic collaboration with BhabhaEkiertLab at NYU Langone.

(2/n)This work was a tour de force of both theory and experiments on “tiny” yet very important organism in our ecosystem - Microsporidia. Congrats @RayChang0612 and Ari & team interweaving theory & experiments. Back and forth between us & @BhabhaEkiertLab made this a very special

(3/n) Today we all know microbes can cause terrible diseases as germ theory. Where does that idea come from? Pasteur popularized it - but the credit goes to de Lodi - in 1835. As an entomologist; he worked for 25 years trying to figure out what makes silk worm sick..

(4/n) In middle of massive collapse of silk industry in Europe; Lodi demonstrated that a living organism was “contagious” & key culprit making silk worms sick. Rest is history! Eventually Microsporidia were identified & so much work has gone in identifying morphological features

(5/n) But how does this incredible dynamic machine work. That is what we focus on. Since the day @BhabhaEkiertLab showed me some of these movies - we have been hooked. Also read previous work that established the physiological measurements in this system

(6/n) Microsporidia spore (3-4 um) float around in environemnt. It’s estimated almost 60% of all water bodies currently infested with human-infecting microsprodia. It impacts patients with compromised immune systems & are emerging tools for biological control of mosquitoes.

(7/n) So how does this tiny little parasite infect cells. And here comes an amazing biology - believe it or not - it shoots out a tiny “polar tube” 100nm in diameter that is key for infection. Further more, nuclear material is shot through this 100nm tube. So many questions..

(8/n) Instead of biochemical - we started by exploring biophysical picture. For years - a lot of confusion existed on how this tube shoots out. As many have previously shown - this is NOT “jack in the box”. In this story, we focus on topology, energy dissipation & hydraulics.

(9/n) A puzzle Ray and I started with - what is the topological connectivity of various organelles in this parasite. If you ever play with a "Klein bottle" - you know that the orientability of surfaces can be complex. Is the the material inside the polar tube inside or outside?

(10/n) Once you think about connectivity of all the key organelles, only a few possible topological linkages survive as being compatible. This led to a set of testable hypothesis.. where theory leads the design of experiments, not the other way around.

(11/n) @BhabhaEkiertLab focused on utilization of highres-EM imaging; & generated incredible ultrastructure images. Just look at them - with the folded polar tube inside and shot outside the spore. Starting point for testing these hypothesis.

(12/n) By running experiments in various viscosity (without dramatically changing osmotic pressure), we can explore where does energy dissipation in this extreme event come from and sets the limits for the eversion process.

(13/n) Read the paper for details - its amazing even in 100nm tubes, the continuum predictions still hold. We account for lubrication, eversion of the tube and pressure associated with such fast dynamics.

(14/n) The paper provides not only energetics of polar tube (which turns out to be eversion) but also how a new process (buckling of the shell) enables shooting the nuclear content out of the cell. This is a new idea that only arose as a dialog between theory and experiments!

(15/n) Lots of hidden gems in the paper - take a look and we would love to hear ideas and feedback. Overall, this work builds on growing interests in “cellular hydraulics” and takes it to an extreme geometry. These organisms inspire and remind us not to ignore geometry.

(16/n) With @BhabhaEkiertLab - we will continue testing many new ideas proposed in this paper. Special shout-out to @RayChang0612 (a real doctor in my lab) who lead much of the theory work in my lab and Ari in Gira/Ekiert lab who lead structural work. Incredible individuals!

(17/n) Next time you think about a cell - do think about all the extreme processes outside our sense of perception which are fundamental to everything they accomplish. So much new physics and biology to be discovered - only if we look at the tree of life as a whole.