Ultra-fast Biophysics
ABSTRACT
Many ultrafast phenomena with extreme acceleration can happen at a cellular scale. While there is no consensus on how much acceleration can we call it "ultrafast," one common gauge we use is the acceleration of the cheetah, the fastest land animal, which can reach up to 1.5 g.
At cellular scale, special concerns need to be considered when evaluating acceleration in a low Reynolds number context, as the inertia is often negligible at cellular scale motility and motions can abruptly stop with seemingly high deceleration. By studying a large number of biological systems, we are establishing the fundamental limits of ultra-fast movements at cellular and sub-cellular scale.
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Topological damping in an ultrafast giant cell - https://www.pnas.org/doi/abs/10.1073/pnas.2303940120
Energetics of the Microsporidian Polar Tube Invasion Machinery - https://elifesciences.org/reviewed-preprints/86638/reviews
Entangled architecture of rough endoplasmic reticulum (RER) and vacuoles enables topological damping in cytoplasm of an ultra-fast giant cell - https://www.biorxiv.org/content/10.1101/2021.12.13.472465v1
Collective intercellular communication through ultra-fast hydrodynamic trigger waves -https://www.nature.com/articles/s41586-019-1387-9
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BIG QUESTION
“Can cells out-perform a cheetah in its act? ”
What is Spirostomum ambiguum?
Spirostomum is a giant single-cell ciliate growing in brackish water. They can grow up to 1-4 mm, and you can see them with your naked eye, even dwarfing many animals! Also, do you know that these cellular giants can contract themselves to less than half of its original body length in just 5 msec, creating an acceleration of 15 g? (We human in upright sitting position can only tolerate 5 g). This extraordinary ability makes them one of the fastest single cell organism!
Diagram of the anatomy of Spirostomum ambiguum, in relaxed (left) and contracted (right) states. Ci, cilia; cs, cytostome; ex, extrusomes containing toxins; fv, food vacuoles; mi, micronuclei; ma, macronuclear nodules; sg, somatic grooves. Drawings made by M. Gruber.
What specific things are we studying about Spirostomum?
The combination of extreme cell size and extreme acceleration in the same species makes Spirostomum a perfect model organism to study many exciting questions about the extremes of cell biology. Why do they need such a high acceleration for their contraction? How can they survive a 15g acceleration? What are the intracellular organization that allows them to survive? Can we theoretically and experimentally analyze the energy dissipation process? How long does it take for the molecule to travel from one end of the cell to the other? Does the contraction make the substance transport process faster? We use both theory, experiments and high resolution imaging techniques to answer these questions.
Collage of a spontaneous contraction and recovery, without electric stimulation.
Data
So far, we have discovered that Spirostomum ambiguum can utilize the ultrafast contraction to generate water pulse waves, and they can communicate with each other through the water pulses. This demonstrates a novel way of cellular communication that was not known in the past.
Recently, we also discovered a unique entangled architecture of rough endoplasmic reticulum and vacuolar meshwork inside the cell, and we used simulation techniques to demonstrate that this entangled architecture can transform the cytoplasm into a strain-induced jamming material that allows the extreme acceleration to be dampened, allowing the cell to undergo multiple contractions in their lifetime without damaging themselves.
(left) Trigger wave propagating through a colony. The connecting lines and colors indicate which organisms triggered which other organisms. (center) Confocal imaging of the endoplasmic reticulum (ER) and the vacuolar meshwork of a contracted organism and a cropped magnified region (top right). The image shows a fenestrated web-like structure of ER wrapping around vacuolar meshwork throughout the entire organism. (bottom right) 3D schematic drawing of the entangled topology between fenestrated ER and vacuoles.
Project status
Our lab is continuing work on Spirostomum ambiguum to understand other aspects of its biophysics.
This work is currently funded by the NSF CCC (Center for Cellular Construction).
What is a microsporidia?
Microsporidia is a group of eukaryotic, obligatory, intracellular parasites that can infect various animals, including human. In fact, their first discovery in mid-19th century was because of the investigation into the mysterious collapse of silkworm industries in France and Italy! Even nowadays, microsporidia continue to cause huge economic burden in shrimp farming and beekeeping industries, and cause many debilitating diseases in immunocompromised patients. They establish infection through spores, and the spores contain a prominent, coiled organelle called the polar tube (PT). Once the spores encounter the appropriate environment for germination (for example, our digestive tracts), they shoot out PT at ultrafast speed (up to 300 µm/sec), and the PT also serves as a conduit for the infectious cargo.
Overall organization of organelles in an A. algerae spore.
What specific things are we studying about microsporidia?
Note that despite the ultrafast speed of the process, the spores do not contain functional mitochondria, meaning that there is no active production of ATP during the infection process. Considering the extremely narrow cross-section of PT (only 100-nm-wide) and the huge resistance associated with a narrow tube, it is not known how much energy is required for this process, and also how can the spore generate enough energy for it.
Examples of slices from SBF-SEM imaging and the corresponding 3D reconstructions for ungerminated, incompletely germinated, and germinated.
Data
To decipher the topological connectivities and geometry at the organelle scale, we combined extensive volume EM (serial block-face scanning electron microscopy) 3D reconstructions of single spores in ungerminated, incompletely germinated and germinated states with theoretical enumeration of all possible topological connectivity graphs of various organelles as imaged in 3D. By performing biophysical calculations on energy dissipation in various processes including polar tube extension, fluid/cargo transport through a narrow tube and lubrication theory of various elements moving past each other, we enumerate energy and power requirements of polar tube ejection process. Finally, we validate our theoretical models for energy dissipation with a wide range of polar tube germination experiments in various external fluid viscosity.
Project Status
Our lab is continuing work on microsporidia to understand other aspects of its biophysics.
Collaborators
Bhabha/Ekiert Labs, NYU School of Medicine
