Using Fluorescent Microgel to Detect Cellular Compressive Forces

A group of researchers has recently developed a potential method for measuring compressive forces in and between tissue layers using fluorescent microgels. Scientists have long suspected that mechanical forces play a role in cellular function but have never had a means of quantifying these compressive stresses. With their innovation, the NIH-funded research team may have solved this issue.

The researchers, led by Ning Wang of University of Illinois at Urbana-Champaign, call this technique the elastic round microgel method. Using a droplet microfluid device, they can create microgels in various uniform sizes and inject them into a sample. The outer layer of the droplet is made with alginate, a component of brown algae cell walls. This material cannot be broken down by mammalian cells and is biocompatible with them as well, therefore the cells divide and interact around the microgel as if nothing is there.

Researchers can observe a tissue sample over time and visualize forces and motion via the fluorescent nanoparticles in the microgel. Knowing the microgel’s physical properties, the researcher can calculate forces exerted on the microgel surface, such as compression, tension, and shear force.

The team has already put their microgel to the test, analyzing its interaction with melanoma cells from a mouse. They extracted and cultured a melanoma cell in vitro and found that compressive forces were constant as the cell proliferated from one to one-hundred cells, however when used to analyze cancerous tissue they found that the compressive forces varied over time. These results, shown in the animation above, allude that there is still much to learn about compressive forces and their impact on malignancy.

In addition to studying malignancy, the researchers have also used the microgel to study embryonic development in zebrafish. They injected the blastula-stage embryos with the fluorescent microgel and tracked forces throughout development. Researchers found that three different microgels that were in close proximity of one another experienced very different tensile and compressive forces, and that one single microgel experienced great variation in traction. The team notes that these results not only show the variation in force distribution during embryonic development, but that the fluorescent microgel method can detect dynamic stress changes in living tissue as well.

3D plots of tractions in the 3 microgels.

Sources: NIH Director’s Blog, Nature