The Intersection of Biology and the PlayStation: How Spheroid Coatings Parallel Virtual Reality Gaming

By Guantam Ray

Imagine you’re a video game player circa 2013. Growing up, you played your Mario Kart Wii on a 2D television: you could play in real time, but you could never truly experience the feeling of being there. When your mom announces she’s getting you a virtual reality headset, everything seems to change. Now, you are actually there, side-by-side with the characters. This phenomenon does not only apply to video games, but has extended itself to myriad other fields, one being molecular biology.

When scientists culture cells in the traditional manner for therapeutic applications, they culture them on 2D flat plates. Though these plates are accessible and easy to culture, they are restricted by their 2D nature. When testing therapeutics against these cultured cells, they are not able to fully simulate our internal body conditions, which are much more complex than traditional 2D flasks (Kapałczyńska et al., 2016). This is partly due to the fact that the cells adhere completely to the plate in a single layer, causing a flat and unrealistic standard.

So, how can we culture cells to stimulate real bodily conditions? We can use a spheroid coating that transforms cells into spheroid-like shapes, making them three-dimensional and thus able to mimic our internal body. Though there are several examples of possible coatings used to form these cell spheroids, one coating becoming more readily available by the day is Elastin-like Polymer-polyethylenimine (ELP-PEI). ELP-PEI uses the natural charge of the cells against the coating to simulate cell aggregation and an anchor for structures. What makes it unique is that it combines two different coatings that work together. (Cobb et al., 2021).

In this dual coating, the polyethylenimine (PEI) is used for the actual cell aggregation: the positive part of the polar PEI molecules attracts the negatively charged parts of the cell wall, and repels the nonpolar and positively charged parts of the cell. This causes the cells to aggregate into lumps that convert them into adopting a 3D form. Meanwhile, the ELP allows for firm attachment to the cell plates used for coating, as the elastin-like nature makes the cells more flexible and thus more easily conforming as a molecule.

So, the coating works in a bimodal manner to result in a product that allows for both cell spheroids to aggregate, forming a 3D structure, and for the cells themselves to attach to the plates. The cell attachment here is crucial as it enables the therapeutics to be easily tested in a way that mimics our body, where our cells directly attach to our skin rather than “float” around within our skeleton. These 3D spheroids allow for numerous applications in the biomedical world. Most significantly, these spheroids can be grown in a manner to simulate overgrown cells, which are the precursor to cancerous tumors. As a result, scientists are able to better simulate small cell tumors within the lab, which then allows for better accuracy when finding therapeutic treatments (Zhou et al., 2024).

However, the benefits extend beyond cancer research, as the spheroid formation in general allows for better simulation of body-like conditions. The coating will allow scientists to find an easy, accessible method to better simulate body-like conditions for numerous diseases, from Alzheimer’s to E. coli. Moreover, the technique promises further applications within testing everyday cell processes like cell signalling and mitosis, so the coating will enable further applications beyond disease therapeutics into our daily lives.

References

Cobb, J. S., Rourke, A. S., Creel, A., & Janorkar, A. V. (2021). 
Manipulating the solution environment to control the surface roughness of elastin-based polymer coatings. Journal of Biomaterials Applications, 36(3), 419–427. https://doi.org/10.1177/0885328221101030

Kapałczyńska, M., Kolenda, T., Przybyła, W., Zajączkowska, M., Teresiak, 
A., Filas, V., Ibbs, M., Bliźniak, R., Łuczewski, Ł., & Lamperska, K. (2016). 2D and 3D Cell Cultures – a Comparison of Different Types of Cancer Cell Cultures. Archives of Medical Science, 14(4). https://doi.org/10.5114/aoms.2016.63743

Zhou, T., Wen, Y., Wu, Z., Song, S., Wu, B., Guo, H., Chen, H., Feng, X., 
Mu, L., Lu, X., Ji, T., & Zhu, J. (2024). Dual-bonded polyethyleneimine network with electron-withdrawing groups at α, β-sites for ultra-stable and low-energy CO2 capture in harsh environments. Green Energy & Environment, 10(5), 1039–1049. https://doi.org/10.1016/j.gee.2024.10.005