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Bacteria don’t just go with the flow

Stanford postdoc Arnold Mathijssen wanted to know how bacteria swim upstream. Someday, his findings could shape how we design devices and deliver drugs.

What Arnold Mathijssen, PhD, and colleagues see through the microscope seems improbable -- wriggling, wiggling bacteria struggling to swim against the current flowing through a tiny channel.

It's the sort of behavior we're used to seeing from salmon, not microbes. But scientists have long known that bacteria can swim against currents.

Those upstream swimmers can cause problems when they wend their way into medical devices. For example, 75% of hospital urinary tract infections occur in catheters, despite their outward flow of urine, according to the Centers for Disease Control.

Understanding how bacteria swim upstream could help researchers design medical devices that thwart their progress. Mathijssen and collaborators used a microscope to precisely track individual E. coli swimming in liquid growth media flowing at different speeds. Their insights could lead to biomaterials that stymie bacteria's upward march and, one day, synthetic materials that travel upstream to deliver drugs.

The findings appear in Nature Communications. Mathijssen, the study's lead author, is a postdoc in the lab of Manu Prakash, PhD, associate professor of bioengineering.

The study, conceived during Mathijssen's time as a graduate student at the University of Oxford, was a collaboration between Stanford, the ESPCI Paris in France and the TU Wien in Austria.

To track bacterial responses to flowing current, the researchers monitored E. coli in microfluidic channels 100 microns in diameter -- about the width of a strand of hair. They then steadily ramped up the rate at which media flowed through the channels in much the same way that a professional swimmer might dial up the current in a training pool.

When the media flowed along at a glacial pace, the bacteria swim around in circles. But as the flow quickened, they started to swim headlong into the current. It's unclear why bacteria evolved to do this, though Mathijssen suspects it helps them access safer, resource-rich environments.

"Bacteria have been around, of course, from the beginning and have always had to live in very diverse flow conditions," said Mathijssen. "We don't know, from the point of view of a cell, why they want to go upstream. But presumably it's to find a niche where they can get to first and predators cannot get to as quickly."

While the "why" behind upstream swimming remains an open question, Mathijssen and colleagues were able to pin down the "how." Flowing media causes the bacterial tail, known as the flagellum, to flip direction like a weathervane in the wind.

A beating flagellum takes on a coiled, spiraling shape -- a bit like a spring or, depending on how hungry you are, curly fries. Because of the direction of that spiral, the bacteria Mathijssen observed moved forward while also veering slightly to the right.

In the future, Mathijssen envisions biomaterials with microscopic leftward grooves that block right-drifting bacteria in their tracks. 

"Engineering techniques are getting really good these days. You can create obstacles that rectify the motion of the swimming cells," said Mathijssen. "We know how to do this in a lab setting. Now, the question is, 'Can it be done affordably around the world?'"

But Mathijssen has bigger ambitions than simply stopping bacteria. He is working on using the mathematical models he's developed to understand bacterial swimming and design what he calls synthetic microswimmers -- microscopic particles or liquid droplets endowed with chemical or magnetic properties that allow them to move upstream. These efforts are at an early stage, but microswimmers could conceivably be used to deliver drugs in the face of opposing currents, such as in the bloodstream.   

"The first question is, 'How can you control navigation at the microscale' and the second question is, 'How can you put something inside?'" said Mathijssen.

Image by Arnold Mathijssen

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