Tufts Engineers Uncover Novel Mode of Cell Migration

Influencing cell movement within fluid environments opens new possibilities in nanomedicine and bioremediation

Researchers have long dreamt of the day when tiny robots would be able to swim inside our bodies to fix things that go wrong, kill cancer cells, and deliver medicine, just like in the movie Fantastic Voyage, in which a submarine crew is shrunk down to treat a blood clot. While researchers aren’t exactly following the Hollywood script, they are making strides in fields such as nanomedicine and bioremediation.

Nanomedicine is the application of nanodevices—machines and biological devices engineered at the nano-scale—to deliver drugs, improve imaging and sensing, and repair damaged cells and tissues.

Researchers in the field have started designing microrobots that are able to swim through the body, but these robots require complex fabrication and an energy source. What if researchers were able to harness nature’s own version of a microrobot—swimming cells—and could direct these cells to specific areas within the body?

Jeffrey Guasto, an associate professor of mechanical engineering, and colleagues from his laboratory at Tufts are developing the fundamental knowledge that could be applied to improve the navigation of swimming cells within arteries, veins, and tissues—as well as to understand how cells migrate within the Earth’s sediments and soils.

They use principles from fluid mechanics, biology, physics, and math to observe and characterize the ways in which fluid flow, geometry, and chemical signals influence the transport of swimming cells.

“A lot of the work that we do in the lab deals with swimming cell migration and navigation,” says Guasto. “How can we determine where cells are going to end up if they are directed to swim against the blood stream or in the turbulent ocean? How do cells navigate within very dynamic and porous fluid environments?”

Controlled Conditions

To investigate these questions, Guasto utilizes microfluidic devices—small devices that can be designed to approximate the conditions of human tissue, soils, and sediments. The lab sends fluids and cells through these devices under a variety of controlled conditions, including varying flow speed and geometry.

These tools allow the lab to model complex three-dimensional spaces, to precisely control the fluid’s velocity within those spaces, and to use detailed imaging to visually capture how the cells move.

A recently published report in Nature Communications by postdoctoral scholar Nicolas Waisbord, Amin Dehkharghani, EG17, EG21, and Guasto describes how they used these devices to identify a novel way of trapping cells within porous materials in conditions similar to human tissues, sediments, and soils, with implications for drug delivery and pollution remediation.

In their work, the researchers orient bacterial cells that take their directional cue from magnetic fields to swim upstream against controlled fluid flows through a series of pores within the microfluidic devices.

The cells exhibited three distinct transport tendencies: they overcame the flow and traveled upstream; they were swept away by the overwhelming strength of the flow; or they became trapped in vortical orbits near the pores.

Factors That Influence Cell Migration

The researchers found that fluid velocity, the strength of the directed cell movement, and the geometry of the pores all combined to influence cell migration.

“What we observed is that while the flow competes with the directed swimming of the cells, the trapping is not just a result of a stalemate between those forces,” says Guasto. “The cells are actually trapped in particular areas over a broad range of conditions due to the pore geometry.”

The ability of cells to take up residence in an otherwise flowing system is crucial to many biological, ecological, and potentially engineering processes. For example, cells could be tasked with delivering medicine to a specific area within the vascular system or they could be injected into the ground to absorb pollutants.

Getting these cells to travel to a particular location, having them remain in place for a set duration, and then flushing them out with a strong fluid flow opens the door to new medical and bioremediation strategies.

“If you wanted to use bacteria to break down pollutants from a chemical spill, for example in soil, understanding their retention and how fast the cells need to be pumped is critical to get them to a desired location,” says Guasto. “You also need to know how the environment’s geometry and the orientation of the cells influences their movement.”

Guasto and his colleagues continue to advance their knowledge in these fields. Although microfluidic devices offer insights into cellular transport in a variety of conditions, most experiments are limited to two-dimensional systems.

The lab’s work hints that these phenomena exist in more realistic three-dimensional systems as well. Recent publications explore complex flow topology within porous media, the effects of fluid viscosity gradients on cell movement, and the transport of active and complex materials in porous media.

“We’re trying to make more realistic systems that represent what is happening in the natural porous environments, while still having precise control over the experiments,” says Guasto. “So far, we have added physical complexity in the form of geometry and flow, and now we are expanding the biological complexity of these model systems by considering directed movement to the cells.”

Isaac Nicholas can be reached at isaac.nicholas@tufts.edu.

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