How does a cell swim fowards?

“Why are they swimming backwards?” This is one of the most common questions I get asked whenever I show a video of Leishmania parasites swimming.

Swimming Leishmania at 200 frames per second (8× slower than actual speed)

If you look at Leishmana with a high speed video it's easy to see they tend to swim 'tail-first', with the flagellum sticking forward into the direction of travel. Sperm, probably the best-known swimming cells, do the opposite, and swim 'head-first'.

Sperm on the left, Leishmania on the right

Of course, if you could ask the Leishmania, they'd say that they're swimming forwards and it's the sperm which are swimming backwards. This raises the question of how does a swimming cell decide which direction it should swim? Which direction is forwards?

The direction a cell swims depends on the waves which travel down the flagellum. If they start at the base and go towards the tip then the cell will swim head-first. If they start at the tip and go towards the base then the cell will swim tail tail first. So how do they choose where the waves start?

We answered this question taking advantage of a useful behaviour of Leishmania. If you look closely at the video above you can see one cell is swimming forwards (the cell on the left) and the other is turning on the spot (the cell on the right). And if you look very closely you'll see that the waves in the cell on the left start at the flagellum tip, and the waves in the cell on the right start at the base of the flagellum.

Tip-to-base on the left and base-to-tip on the right.

This let us use genetic tools to try to break one direction of flagellum wave without affecting the other and tease apart how the flagellum movement might be chosen by the cell. To cut a long story short, we found differences in the motor proteins between the base and tip which seem responsible. Interestingly, similar differences turn up in many organisms, including human sperm, suggesting it might be a general pmechanism. You can read all about this in our recent paper: At the PNAS website or as a PDF.

https://doi:10.1073/pnas.1805827115

Looking at the structure inside cells

How complex and structured is the inside of a cell? It's hard to imagine, but the internal organisation of cells is typically precisely controlled by molecular skeletons and scaffolds, giving cells the shape they need to function.

We can discover the 3D organisation of the inside of cells using electron tomography; a process where you capture a series of images with an electron microscope, with the sample tilted at a slightly different angle for each image. This can then be used to calculate the 3D shape of the sample, using the same maths as for an X-ray CT scan.

Leishmania parasites are exquisitely structured. While they are only 2 micrometres wide (100 would fit across a human hair) they have a precise internal organisation which they faithfully replicate each time they divide. One of the distinctive parts of this organisation is the flagellar pocket, where the cell membrane folds in on itself at the base of the whip-like flagellum that the cell uses to swim.

In my latest paper, "Flagellar pocket restructuring through the Leishmania life cycle involves a discrete flagellum attachment zone", I used electron tomography to reconstruct the three-dimensional organisation of the Leishmania flagellar pocket. The structure in this area of the cell is incredible, and the journal picked a rendering of it for the cover image.

Volume covered in this 3D reconstruction is only 3 by 2 by 1 micrometres, about the size of a typical bacterial cell, but has enormous complexity. I have shown the microtubules (which make up most of the cytoskeleton) in red and membranes in blue. Each microtubule is only about 5 molecules wide, and is about 10,000 times narrower than a human hair! Some other specialised parts of the cytoskeleton are in green.

You can download the paper for free here to take a look at the structures in this area of the cell in more detail.

Software used:
IMod: Electron tomography structure
Blender: Tidying and rendering of the 3D structure