The lotus leaf is a pioneer in the field of self-cleaning and water repellency. Water droplets practically float on its surface, whose unique texture traps air in its nano-sized ridges and folds.
Rice University bioengineers report that they have harnessed the lotus effect to develop a cancer cell cluster culture system that can shed light on hard-to-study tumor properties. The new zinc oxide-based culture surface mimics the surface structure of the lotus leaf, providing a highly tunable platform for high-throughput generation of nanoscale, three-dimensional tumor models.
The superhydrophobic array device (SHArD) designed by Rice bioengineer Michael King and collaborators can be used to create tunable, compact, physiologically relevant models for studying cancer progression, including metastasis (the stage of disease in which cancer cells travel through the bloodstream from a primary tumor site to other parts of the body).
“The study of metastasis, the leading cause of cancer death, poses a particular challenge in part because of the difficulty of developing accurate, high-throughput models,” said King, who is the corresponding author of a study published in Nano ACS describing the new breeding platform. “We hope this tool will allow us to gain new insights into this problematic stage of the disease and help us identify ways to intervene to stop or prevent it.”
Scientists and clinicians now rely on blood samples containing circulating tumor cells (a key marker of metastasis) to understand the properties of primary tumors as well as the causes of cancer spread. This sampling method, often referred to as “liquid biopsy,” often does not produce a sufficient “catch” to allow for in-depth, large-scale studies of metastatic processes.
“‘Safety in numbers’ unfortunately also applies to cancer cells circulating in the bloodstream,” said Alexandria Carter, a researcher in King’s lab and co-author of the study. “Cancer cells traveling alone are more likely to succumb to destruction by shear stress or attacks by immune cells. However, when they travel in groups, the likelihood that they will successfully arrive and take up residence in other parts of the body increases.
“Such a few solitary cancer cells in a single blood draw are already rare, so isolating enough clusters for detailed study is especially challenging. That’s why SHArD is an exciting new tool for understanding primary and metastatic cancer.”
King’s lab had previously succeeded in creating layers of halloysite nanorods, a natural substance whose texture promotes adhesion of circulating tumor cells while repelling blood cells.
“When Kalana Jayawardana joined our lab as a new postdoctoral researcher in 2018, he began experimenting with growing zinc oxide nanorod surfaces,” said King, a Texas Cancer Prevention and Research Institute scholar who recently joined Rice as the E.D. Butcher Chair in Bioengineering and special adviser to the provost on life sciences collaborations with the Texas Medical Center. “At first, we didn’t have a specific application in mind, but we were curious and hopeful that the new material might have special properties that would be useful for cancer biology.”
The project was later taken up by a PhD student in King’s lab, Maria Lopez-Cavestany, and took an exciting turn. Cavestany, now a PhD student, is the first author of the study.
Once they had managed to create a stable “carpet” of zinc oxide nanotubes, the researchers added a Teflon-like coating on top, essentially recreating the structure of the lotus leaf: nanoscale roughness combined with a hydrophobic layer that together gave rise to true superhydrophobicity, a word that comes from Greek and means “extreme fear of water.” To create SHArD, the researchers added a grid of microwells with perfectly sized compartments, then tested the system to evaluate its performance.
“SHArD is ready to be used in biomedical research,” Carter said. “Any lab with access to a clean room can follow our protocols and create versions of this platform that exactly meet the needs of their specific research projects.”
Initially intended as a means to reliably grow primary tumor models at higher throughput, SHArD is highly tunable and can be easily adapted to grow metastatic clusters as well. The fact that SHArD has been successfully used to grow spheroidal models of primary tumors already expands the cancer modeling toolkit, making it possible to create superhydrophobic culture devices in the absence of highly specialized equipment.
“The cluster-forming device has opened the door to new areas of research into the dangerous clusters found in the bloodstream of patients with advanced cancer,” King said.