For years, cancer research has revolved around targeting genetic mutations, membrane receptor proteins, and cell signaling pathways. But what if the key to understanding cancer lies not just in its biochemical components but also in the physical structures that shape its behaviour? Enter a groundbreaking approach led by IDMxS PI, Asst Prof Wenting Zhao, who is turning our perspective of cancer cells on its head. By focusing on the physical shape of cells and the tiny clusters of proteins they host, this research is unlocking a whole new frontier for cancer diagnostics and treatment.
Why Shape Matters: The Myth of the “Flat” Membrane
For decades, most scientific models assumed that a cell’s membrane is flat. Researchers would study how proteins behave, signal, and cluster on this imagined flat surface. But here’s the reality: cell membranes are never flat. Real cell membranes bend, curve, and fold continuously. These curves are not just random quirks—they’re active participants in cellular processes. They change dynamically as the cell moves, communicates, and adapts to its environment.
Here’s where things get interesting: one of the most notorious proteins involved in cancer is Ras, a key player in cell growth, division, and survival. Ras proteins are known to cluster on the membrane to send signals, but recent research has revealed a surprising twist: when the membrane curves, Ras proteins cluster more frequently and with greater intensity. Imagine it like a popular restaurant located on a busy street corner—its unique position naturally attracts more people, just like the membrane’s curve draws Ras proteins to cluster more intensely. For scientists, these curves become hotspots, not just for protein activity but for scientific discovery.
How Nanobars Create Controlled “Hotspots” for Protein Clusters
But how do you study these hotspots if they’re constantly changing? To isolate these hotspots, Asst Prof Zhao and her team built nanobars—tiny, nano-sized structures that force the cell membrane to curve in a controlled way. When cancer cells are grown on these nanobars, the Ras proteins naturally gather around the curved regions. This clustering doesn’t just make it easier to study the proteins; it creates a readable, quantifiable pattern.
This method allows researchers to visualise and quantify how Ras proteins behave in an environment that mimics a real cell’s natural conditions. Clusters in real cells are too small for traditional microscopes to detect, but by creating hotspots with nanobars they’re turning an “invisible” process into something that can be seen and studied. The potential for cancer drug screening is enormous—scientists could now watch in real-time as drugs attempt to break up these Ras clusters.
Morphology Matters: The Shape of the Nucleus Tells a Story
Building on these findings, Asst Prof Zhao pushes this research even further. When diagnosing cancer, pathologists often look at the shape of the cell’s nucleus. If it’s smooth and rounded, the cell is typically non-malignant. But if the nucleus is misshapen, wrinkled, or folded, it’s a sign of malignancy.
The problem is that it’s largely subjective. Different pathologists may see the same image and give a different diagnosis. Even AI-based image analysis systems are sometimes unreliable because most pathology slides aren’t detailed enough to give the AI sufficient data. This means AI systems can be inaccurate without consistent, high-resolution image data inputs.
To solve this, Asst Prof Zhao has begun using nanopillars to “guide” the shape of the nucleus, forcing it to deform in specific ways. Malignant cancer cells and non-malignant cancer cells respond very differently to this process. Here’s the key insight from Asst Prof Zhao’s research:
- Low-malignant cancer cells deform into smooth, circular rings around the nanopillars.
- High-malignant cancer cells deform into lines or elongated shapes along the nanopillar array.
This difference is crucial. For the first time, researchers have a way to measure nuclear shape changes in a precise, quantifiable manner. No more guesswork or pathologist “experience-based” grading. These patterns can be directly linked to cancer cell behaviour, including their ability to migrate. Taking breast cancer cell as an example, cells that form line-shaped deformations migrate faster and further, while cells that form ring shapes migrate more slowly.
Why This Approach Could Change Precision Medicine
When it comes to cancer diagnosis, we’re used to thinking about genetics, mutations, and protein markers. But this new approach invites us to think differently. It’s not just about “what” cancer cells are made of—it’s about how they’re physically shaped and organised in high precision.
By creating physical, measurable patterns using nanobars and nanopillars, Asst Prof Zhao’s team is moving beyond qualitative judgments and into the realm of quantitative analysis. Here’s why that’s revolutionary:
- More accurate cancer grading: Instead of subjective visual assessments, pathologists could rely on clear, measurable patterns. No more “maybe a 3, maybe a 4″—they’d have objective data to back it up.
- New methods of drug screening: Using nanobars, drug developers could see how drugs affect Ras clustering in real time. Does the drug break up clusters? Does it change the nuclear deformation? This data could dramatically speed up drug discovery.
- Unravelling cancer’s complexity: Cancer isn’t one disease. It’s a collection of thousands of different cell behaviours and mutations. This method reveals cell-to-cell variability—that is, how cells within the same tumour behave differently from one another.
What’s Next? The Future of Cancer Research
This innovative strategy for uncovering unconventional cancer targets is only beginning to unfold. As nanostructures become more sophisticated, Asst Prof Zhao and her team will be able to fine-tune the curvature and arrangement to study even more aspects of cancer cell behaviour. Imagine nanopatterned devices being used directly in pathology labs, providing on-the-spot quantitative data for cancer diagnosis.
As for drug development, the concept of “watching” Ras proteins cluster and disperse in response to treatment opens new doors. Pharmaceutical companies could use these nanobar-guided assays to screen drugs faster, better, and cheaper than ever before.
Conclusion: Shaping the Future of Cancer Research
Cancer has long been seen as a molecular disease driven by rogue proteins and genes. But this new perspective reveals that its physical shape and cellular architecture are just as important. By focusing on non-conventional targets like membrane curvature, protein clustering, and nuclear deformation, Asst Prof Zhao and her team are introducing a radical shift in how we study, detect, and treat cancer.
We’re no longer limited to looking at cells on a flat plane. By embracing the natural curves, twists, and wrinkles of real cells, science is finding new ways to outsmart cancer. It’s a timely reminder that sometimes, the answers aren’t found in what’s obvious—they’re found in what’s been hiding in plain sight all along.
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