In a new study published in Nature Methods, researchers from Northwestern University and The Ohio State University have introduced a technology called LEVA (light-induced extracellular vesicle and particle adsorption). This tool allows scientists to arrange extracellular vesicles and particles (EVPs) in precise patterns on surfaces, offering new ways to study how cells communicate.
Extracellular vesicles are tiny biological packages that cells release into bodily fluids and tissues. These vesicles carry proteins, RNA, and other molecules that help cells send messages related to processes such as wound healing, infection response, tissue regeneration, and cancer spread.
LEVA uses ultraviolet light projected onto an array of mirrors to create stencil-like patterns on a surface. The exposed areas become adhesive for EVPs while unexposed regions remain neutral. When EVPs are introduced, they attach only to the sticky regions, forming specific shapes such as dots or trails. This approach enables researchers to mimic the way these vesicles might be arranged naturally within human tissues.
Colin Hisey of Northwestern’s McCormick School of Engineering co-led the work with Xilal Y. Rima and Jacob Doon-Ralls at The Ohio State University. Eduardo Reátegui at Ohio State is the senior author of the study.
“Our research provides scientists with a powerful new tool to understand how cells communicate through the ‘breadcrumb trails’ they leave behind during movement in both healthy and disease contexts,” said Hisey. “A better understanding of their role could lead to new treatments for diseases and improved wound healing therapies. The technique’s versatility means it can be adopted by researchers worldwide to accelerate discoveries in multiple areas of human health.”
Previously, most studies examined EVPs suspended in liquid rather than fixed on surfaces. LEVA now allows for controlled experiments where scientists can observe real-time interactions between cells and patterned EVPs. For example, the team used LEVA to create shapes from bacterial EVPs on a surface before adding human neutrophils—white blood cells involved in immune response—to observe their behavior.
The neutrophils rapidly detected the EVP patterns and clustered around them, similar to how they would respond at an actual site of infection or injury inside the body. According to Hisey: “Neutrophils have evolved to recognize the antigens present on bacterial cells and, hence, also bacterial EVPs because they are so similar. Once neutrophils come into contact with and initially sense the EVPs, they undergo dynamic responses that we’re still trying to understand. This is something our platform can help us study.”
Looking ahead, Hisey’s group plans to adapt LEVA for use with more complex three-dimensional materials that better resemble conditions inside living organisms. Their goal is to systematically map how different types of surface-bound vesicles influence cell behavior across various disease contexts—including cancer metastasis, wound healing, and immune responses.
“We want to apply LEVA across multiple disease areas to systematically map how different types of surface-bound vesicles affect cell behavior in various conditions and configurations, with an initial focus on cancer metastasis, wound healing and immune responses to pathogenic EVPs,” said Hisey. “Our long-term goals include developing therapeutic strategies that harness or block these vesicle-mediated cellular communications and expanding the technique to study how nanoparticles interact with surfaces in a purely materials engineering context.”
The research was supported by funding from organizations including the National Institutes of Health; Ohio State’s Center for Cancer Engineering; OK-PROS; LEGACY program; and Burroughs Wellcome Fund.