
“The UN estimates that by 2050, common bacterial infections could kill more people than cancer,” says Arnold Mathijssen, a biophysicist at the University of Pennsylvania who studies how active particles like bacteria move in fluidic systems. “Bacteria are remarkably fast, adaptive swimmers, capable of moving hundreds of body lengths per second while being subjected to strong fluid flows.”
Rather than simply going with the flow, he says, pathogens can actively swim upstream against those fluid currents, a behavior that can lead to severe respiratory, gastrointestinal, and urinary tract infections (UTIs) and the contamination of dental and medical equipment such as catheters.
“But how these microorganisms ‘go against the grain’ through these confined, maze-like environments has remained a mystery.”
How bacteria navigate complex environments
Now, Mathijssen and colleagues have fabricated nanoscale, multichannel tubes that mimic those found inside the body to reveal how the bacterium Escherichia coli (E. coli) travels upstream to invade and colonize spaces.
Their findings, published in Newton, shed light on pathogen motility in complex and often unwelcoming fluid environments, and offer solutions that can be implemented directly in biomedical devices.
“Rather counterintuitively, we discovered that wider channels with faster counterflows are actually more prone to invasion,” says Ran Tao, first author and graduate researcher in the Mathijssen Lab in Penn’s School of Arts & Sciences. “But these incursions can be inhibited effectively with sharp corner designs.”
Key findings on channel design and flow
The team broke down the invasion into four distinct stages, tracked thousands of cells, and combined these data with simulations and mathematical analysis to uncover how bacteria colonize in cavities. In addition, they determined the effect of different conditions—flow strength, channel confinement, corner smoothness—to gauge bacterial proliferation. The combined approach allowed them to predict bacterial flux—the total number of cells moving upstream over time—across different microtube shapes and configurations.
Comparing smooth, rounded corners with sharply angled ones in otherwise identical setups, the team saw how easily bacteria were able to swim against the flow along gentle curves—surfaces that resemble much of the human body—filling those channels quickly. Sharp corners, by contrast, disrupted their motion and stalled their spread, resulting in barely any contamination in angular designs. In thinner channels, bacteria found it much harder to take the crucial first step of escaping from a colonized area to begin their journey against the flow.
This means that devices such as catheters can combine patient comfort—by being thin—with enhanced safety, by having twists and turns, the researchers note.
Unexpected role of fluid flow in colonization
The most surprising results emerged when the team looked at fluid flow itself. Conventional wisdom holds that stronger flow should hinder bacteria trying to swim upstream, slowing them down or washing them away. Instead, the current acted like a guide rail. Bacteria aligned with the flow, rode its structure, and reached upstream locations faster than they could in still or less abrasive conditions.
“Within minutes, we see the first cells arrive all the way upstream,” says co-author Suya Que, an undergraduate researcher in the School of Engineering and Applied Science. “Once they’re there, those early pioneering cells seed new colonies and create a ‘two-way’ invasion that advances from both ends.”
Rather than colonizing cavity by cavity, like a careful burglar checking each room, bacteria rapidly swim all the way upstream and then help themselves to the whole building. After reaching the front, they form streamer-like bioaggregates that are transported downstream by the flow, rapidly seeding the full length of the device and producing a roughly threefold increase in colonization speed.
Clinical implications and future applications
Tao says that this has profound clinical implications for infections like UTIs, because the presence of bacteria in a lower part of the urinary tract may signal a much wider problem, possibly higher up in the kidneys, before symptoms fully register. Flow does not protect the body by default, and under the wrong conditions, it can accelerate the problem.
These findings open doors beyond infection prevention, Mathijssen notes. The same principles could guide the design of microrobots that swim against currents to deliver drugs precisely where they are needed, borrowing strategies honed by bacteria over billions of years.
“The mechanisms that they use to reorient against the flow direction and to swim upstream are very similar to that of a microrobot,” says Mathijssen. “I think this is a very exciting area in biomimicry—learning from biology—that could help us create better biomedical tools and potentially new therapeutics.”
More information
Ran Tao et al, Invasion of bacteria swimming upstream into microstructured devices, Newton (2026). DOI: 10.1016/j.newton.2025.100337
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