The lotus leaf is a pioneer in the field of self-cleaning, water-repellent technology. Water droplets almost float on the surface, whose unique texture traps air in the nano-sized edges and folds.
Bioengineers at Rice University report that they have harnessed the lotus effect to develop a system for growing cancer cell clusters that could shed light on difficult-to-study tumor properties. The novel zinc oxide-based culture surface mimics the surface structure of the lotus leaf and provides a highly tunable platform for the high-throughput generation of three-dimensional nanoscale 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 cancer disease in which cancer cells travel through the bloodstream from a primary tumor site to other parts of the body.
“The study of metastases – the leading cause of cancer deaths – is particularly challenging, in part because of the difficulty in developing accurate, high-throughput models,” said King, corresponding author of a study published in ACS Nano that describes the new cultivation platform. “We hope this tool will unlock new knowledge about this problematic stage of the disease and help us identify ways to intervene to stop or prevent it.”
Scientists and doctors now rely on blood samples containing circulating tumor cells – an important marker of metastasis – to understand the properties of primary tumors, as well as the causes of cancer spread. Often referred to as “liquid biopsy,” this sampling approach typically does not provide enough “capture” to enable 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 the King lab and co-author of the study. “Cancer cells that travel alone are more likely to succumb to shear stress destruction or attacks from immune cells. However, when they travel in groups, the chances of them successfully reaching and settling in other parts of the body increase.
“Those few single cancer cells in a single blood draw are already rare, so isolating enough clusters for a detailed study is particularly challenging. This is why SHArD is an exciting new tool for understanding primary and metastatic cancer.”
The King lab had previously succeeded in creating nanorods from halloysite, a naturally occurring substance whose texture promotes the adhesion of circulating tumor cells while repelling blood cells.
“When Kalana Jayawardana joined our lab as a new postdoctoral fellow 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 ED Butcher Chair or Bioengineering. and Special Advisor to the Provost for Life Sciences Collaborations with the Texas Medical Center. “We initially had no specific application in mind, but we were curious and hopeful that the new material would have special properties that would be useful for cancer biology.”
The project was later taken over by a PhD student in the King lab, Maria Lopez-Cavestany, and went in an exciting direction. Cavestany, now a Ph.D. graduate, is the first author of the study.
Once they were able to grow a stable “carpet” of zinc oxide nanotubes, the researchers added a Teflon-like coating on top, essentially mimicking the structure of the lotus leaf — nanoscale roughness combined with a hydrophobic layer that together give rise to gave rise to true superhydrophobicity, a word derived from the Greek for ‘extreme fear of water’. To create SHArD, the researchers added a microwell grid with perfectly sized compartments and then tested the system to assess its performance.
“SHarD is ready for use in biomedical research,” Carter said. “Any laboratory with access to cleanrooms can follow our protocols and create versions of this platform that precisely 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 growing metastatic clusters. The fact that SHArD was successfully used to grow spheroidal models of primary tumors already expands the toolkit for cancer modeling, making it possible to create superhydrophobic culture devices without 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 late-stage cancer patients,” said King.
