Goldilocks didn’t want to lie down on a bed that was too soft or too hard. Only when the mattress was just right would she rest. It turns out that bacteria behave similarly. A new study by MIT researchers demonstrates that bacteria adhere poorly to soft surfaces and stick to firm ones. The findings challenge conventional wisdom and could hold the key to creating better antibacterial coatings. The researchers have also created soft polymer films that might serve as antibacterial coatings for medical devices and other objects on which harmful bacteria congregate.
Preventing biofilms: Bacteria don’t adhere well to soft polymer films like those in the petri dishes shown here, so the films could be used as antibacterial medical-device coatings. Researchers involved in the antimicrobial work include, from left to right, MIT professors Krystyn Van Vliet and Michael Rubner and students Jenny Lichter and Marciela Delgadillo.
Preventing bacteria from adhering to medical devices is critical to combatting biofilms, a major cause of hospital-acquired infections. Biofilms are sticky, antibiotic-resistant bacterial colonies that commonly form on catheters, the hulls of ships, water-treatment pipes, and even inside the lungs and inner ear. There is no foolproof method for preventing biofilm formation; once they’re established, biofilms are difficult to eradicate because traditional antibiotics can’t get through the films’ sticky secretions to kill the individual bacteria. “Biofilms are such a complicated problem. They’re an incredibly important and ubiquitous thing, yet there’s no really good solution,” says David Weitz, an applied-physics professor at Harvard University who was not involved in the research.
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Biofilms are an area of intense research in microbiology, but until the recent MIT study, no one had tested whether changing the mechanical stiffness of a surface would affect their formation. Krystyn Van Vliet and Michael Rubner, both professors of materials science and engineering at MIT, investigated the behavior of E. coli and a strain of Staphylococcus responsible for many hospital infections. The bacteria were incubated on polymer films whose stiffness was controlled with great precision. Van Vliet and Rubner found that these two very different bacteria shared a sensitivity to surface mechanics. The number of bacteria that will adhere to a stiff surface is orders of magnitude greater than that of the bacteria that will stick to a soft one. And the soft films, created by dipping an object into water-based solutions of biocompatible polymers, “can coat anything,” says Van Vliet.
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“This absolutely goes against the conventional wisdom,” says Wendy Thomas, a bioengineer at the University of Washington. “It’s very exciting.” Only very recently have biologists had sensitive enough tools to study how mechanical forces affect cells. Using atomic force microscopy and other tools from materials science, researchers have investigated questions such as how a blood-vessel cell is affected by the flow of liquid over its surface. But biologists had assumed that bacterial cells, which are simpler than animal cells, didn’t have the internal structures necessary to respond to mechanical stimuli.
Van Vliet says that she and her collaborators spent two years on these studies in order to be certain that they were observing mechanical effects and not something else. “You have to control for all the other regulators of adhesion,” she says, “and catalogue everything about the materials,” including surface charge, roughness, and hydrophobicity.
“What she’s done here is a really careful study to isolate just the stiffness,” says Weitz.
Even after two years of study, Van Vliet says she’s not sure why bacteria adhere better to stiffer surfaces, but it’s a question she hopes to unravel. What is clear is that knowledge of bacteria’s mechanical responsiveness opens up a new approach to engineering antibacterial coatings.
“This is definitely an exciting result and a new factor people haven’t considered,” agrees Helen Blackwell, a chemist at the University of Wisconsin who studies bacterial communication. Other researchers have designed coatings that burst bacterial walls or that are simply so smooth or water-repelling that it’s difficult for bacteria to settle on them. Van Vliet says that these approaches could be combined with her own. For example, the MIT group has already demonstrated that bacteria-killing silver nanoparticles can be embedded in the soft polymers.
Any advance in this area would be good news for patients. Frequently, the only way to remove an established biofilm is to mechanically scrape it off. “But you can’t do that to medical implants,” says Van Vliet.
There’s another side to the MIT work: Van Vliet says that there are situations in which it would be beneficial to use stiff coatings in order to encourage bacterial growth. Most bacteria, including the majority of those living in our bodies, are hard to study because they can’t be cultured in the lab using traditional methods. Blackwell agrees with Van Vliet that investigating materials that promote bacterial adhesion could be a “great way” to approach this problem.
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According to Thomas, the MIT work could “revolutionize” the study of bacteria, and it shows that “we haven’t been seeing a huge part of the picture.”
