A crew of scientists from Montana State University just lately revealed distinctive analysis analyzing how particular person cells reply to viral an infection. The work used state-of-the-art know-how to tradition cells and observe an infection in actual time; it’s the first identified undertaking to make use of microfluidic know-how to tradition, infect and observe an infection on a single-cell degree.

Scientists from MSU’s College of Agriculture and Norm Asbjornson College of Engineering collaborated on the interdisciplinary work, which additionally concerned MSU’s Center for Biofilm Engineering. The outcomes of the undertaking had been revealed final week in Science Advances, one of many nation’s main scientific journals, in a paper titled “Single-cell herpes simplex virus type 1 infection of neurons using drop-based microfluidics reveals heterogeneous replication kinetics.”

The college leaders on the undertaking had been Matthew Taylor, affiliate professor within the Department of Microbiology and Cell Biology, and Connie Chang, who spent practically a decade within the Department of Chemical and Biological Engineering earlier than taking a college place on the Mayo Clinic in Minnesota. Other members of the crew included graduate college students Jake Fredrikson, Luke Domanico and Shawna Pratt, in addition to Emma Loveday, who completed her postdoctoral work whereas concerned within the undertaking and is now an assistant analysis professor within the MSU Center for Biofilm Engineering.

“It was truly a collaborative effort,” stated Taylor. “The engineering ideas and the know-how behind it was all from Connie’s lab. Jake was simply good and had discovered tips on how to develop neurons inside these little gels, principally on a micron scale. Each little bead grew a single cell.”

Those gel beads were created using drop-based microfluidics, a process by which scientific experiments can be carried out on a microscopic scale more quickly and with less expense than through standard means. Chang likened the beads to tiny spheres of gelatin, made of a matrix that allows cells to grow just how they might in a petri dish, but with each individual cell in its own environment.

Fredrikson, who completed his Ph.D. in chemical and biochemical engineering in the spring of 2023, worked extensively on growing neurons – individual nerve cells – inside the tiny beads created through microfluidics. Once that process had been streamlined, the team introduced the cells to herpes simplex virus-1, a common virus that causes cold sores.

“It was basically a tiny tissue made in the lab, where we could infect it and watch virus infection happen in 3D and in real time,” said Chang. “Working with the Taylor lab was like the perfect blend; an engineer and a biologist working together to discover and do something totally new. This is the first time anyone has ever grown neurons at the single-cell level on this type of droplet.”

The particular virus the crew used had a uniquely engineered high quality: It would fluoresce in several colours below a microscope, giving the crew a visible set off as an infection progressed within the particular person cells. When the virus contaminated the cell, it might seem yellow, and when it began replicating – the purpose of viruses inside their host to perpetuate an infection – it turned pink. The cells had been uncovered to various quantities of the virus to look at how they responded.

But not each cell responded the identical method, Taylor stated, which was sudden. While many of the cells turned yellow, not all of them went on to show pink, that means that some cells had been successfully stopping the virus from replicating itself.

“The form of outstanding factor is that each cell was uncovered to an quantity of virus that ought to produce an infection,” stated Taylor. “We know that the cells are contaminated as a result of they’re yellow. Now we’re decoupling the method of an infection from productive replication. We’re kicking the roots of virology, difficult these assumptions of what folks assume an infection means and discovering gaps between what we expect is occurring and what actually is.”

But how and why were some cells able to interrupt the viral replication process? That question will guide extensive future research, Taylor said.

“If cells can naturally shut down herpes viruses, and neurons can control it well, is there something that we can use to further limit productive replication? People have been trying to block herpes infection for eons, unsuccessfully,” he said. “But is there a way that we could shut down the virus and keep it from replicating?”

Further, said Chang, the implementation of microfluidics technology and the team’s first-of-its-kind examination at a single-cell level could create avenues for studying other types of cells, such as brain or lung cells, and examining the cellular response to other infections in search of treatments and cures.

Because drop-based microfluidics enables experimentation on such a small scale, it decreases the cost of research, widening access for scientists to conduct more cutting-edge research at less cost. The potential applications are endless, Taylor said.

“Microfluidics is very adaptable, and if you work with a very talented engineer like we did, they can design all sorts of architecture that can do different manipulations to the process,” he said. “What it really changes is that now you’re using much smaller quantities of everything. You can find rarer cell types, use less primary material and analyze larger quantities with less input.”

It took a collaboration across disciplines to precipitate such a novel accomplishment.

“These are always the best projects, the ones that bridge disciplines, where you’re merging your expertise with somebody else’s expertise,” said Chang. “Those are always the most high-impact, interesting and fun projects, and that’s why I’ve always loved this intersection of biology and engineering, bridging different disciplines.”

Taylor agreed, adding that the project wouldn’t have seen the success that it did without the blend of outstanding graduate students, inquisitive faculty and labs like the Center for Biofilm Engineering that coalesced at MSU.

“I’m most proud of the paper because it really demonstrates the heart of collaboration,” he said. “We just got the right match at the right time for it to be magic, and it really was magic. It was an amazingly productive collaboration.” 

Reference: Fredrikson JP, Domanico LF, Pratt SL, Loveday EK, Taylor MP, Chang CB. Single-cell herpes simplex virus type 1 infection of neurons using drop-based microfluidics reveals heterogeneous replication kinetics. Sci Adv. 2024;10(9):eadk9185. doi: 10.1126/sciadv.adk9185

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