Angie, Glob and the Force

• What’s wrong with you today, Angie? You look puzzled...
• We try so hard to keep our secrets, but they always figure out ways to unravel them… This last thing is just unbelievable, Glob!
• Why? What happened?
• Didn’t you hear the news? They have now figured a way to measure how much force we are able to exert.
• But how? we are so tiny and humans are so big… how can they manage to do that?
• Well, they collect us and put us in Petri dishes with a biomimetic hydrogel and observe us…
• A biomimetic hydrogel?
• Yes, it’s basically a material that mimics our natural environment.
• Oh... I see… these humans and their inventions. But anyways, they can grow us in these hydrogels, but how do they get to measure forces?
• Well, they actually make these hydrogels in a very attractive way. They have proteins that we can hold on to, they include a nice medium where we have nutrients, you name it. But most importantly, they add a substance that triggers us to form new blood vessels!
• What?! They add proangiogenic factors also? Oh Angie, I love proangiogenic factors, they are so delicious! I am missing them so much, I feel like I can’t do much work without them.
• Of course Glob! We are endothelial cells, without them, we can’t form new blood vessels!
• Okay, so humans put us in these super comfy hydrogels, with enough food and even proangiogenic factors. So I guess, then we start forming new blood vessels by holding on to each other, pulling and pushing the hydrogel to make some space. To do this, we indeed need to exert a good amount of forces in the hydrogel, otherwise, we wouldn’t move. But I still can’t imagine how they measure them…
• Well, they also embed thousands of fluorescent spheres in the hydrogel. They are really small, several orders of magnitude smaller than our nuclei. Since they are attached to the hydrogel, when we exert a force and deform it, these spheres also move with it!
• Oh… I see. So they can actually see how we deform the hydrogel just by looking at these spheres.
• Well, they can’t do it with their weak human eyes… apparently, they use a gigantic machine called microscope that is able to take images at a super small scale, enough to see us and the movement of these spheres.
• Wow… that is very small… So I guess that they need to take a couple of images every certain time to see these spheres moving, right?
• Exactly. And finally, they add something that you won’t like…
• You are scaring me, Angie.
• It won’t necessarily kill us but it blocks our mechanical activity. It’s a substance that paralyzes our cytoskeleton blocking our ability to hold onto the hydrogel or exert any force.
• That sounds horrible! Why would they do that?
• I know Glob, but they need to have an image of the hydrogel where there are no forces applied. They need to see a fully relaxed, non-deformed hydrogel. By blocking our movements, the hydrogel, which is elastic, goes back to its original configuration. Then, they image it and compare it to the image that they took when we were exerting forces.
• But they are just humans… how can they track the movement of thousands of spheres? That would take them forever.
• Well, it would… if they didn’t have this other machine called computer.
• Oh! Computers! Yes, I keep hearing about those. Some neurons once told me that humans are always in front of those machines.
• Yes, those things are able to track all these sphere movements in a matter of minutes. With that information and also knowing how stiff the hydrogel is, these machines can also calculate the forces that we were exerting when they took the first image! Think about it: they measure the effects – sphere movements - and then they calculate the causes – cell forces!
• That is very impressive, but I still have some questions. It’s not the first time that humans create new fancy computer functionalities, they do this all the time! I’ve heard that most of the time these are so complex and difficult to use that only few humans can use them. So, why were you so shocked about these news?
• Indeed, you are right. The difference is that this time, a group of humans has made these very complex computer functionalities easy and accessible to most of the other humans! Even for the ones that are not computer experts. This means that more and more human scientists will be able to look at cell forces!
• I see. But now I am wondering. Why do they care about this? It’s not like they can kill our rebel ex-colleagues, the cancer cells, by measuring cellular forces right?
• No, they cannot. But you know how important our mechanics are! Sometimes those rebel cancer cells fool us and secrete proangiogenic factors for us to form a new blood vessel and provide them with blood and nutrients. Only later we discover that they are using us to grow and metastasize to other parts of the body. Let’s face it, humans are much better than us in spotting those rebels. If they find ways to block the formation of new vessels around tumors, they could be helping us in not being fooled by cancer cells anymore.
• Now I get it. We need to exert forces to create new blood vessels, so they want to understand better how much force we can exert and how we do it… that’s why these new technologies are useful for them! I’m also thinking of our mothers, the stem cells. One day I was wondering how stem cells take the decision to turn into brain, muscle, or bone cells during embryonic development. I had the chance to ask one stem cell and she told me that they exert some forces on their surroundings to probe the stiffness of the environment. Depending on how stiff the environment is, together with other chemical factors, stem cells decide to become one type of cell or the other.
• Exactly. That’s just another example of why humans want to understand better how we exert forces.
• Little by little, scientific humans keep discovering more and more of our secrets…
• Yes, Glob. While they still have a long way to fully understand every aspect of our behavior, humans keep impressing me…

About the author:

Jorge Barrasa Fano was born in Madrid in 1992. He studied telecommunications engineering at the Polytechnic University of Madrid and a master's degree in biomedical engineering at KU Leuven. In his PhD, he develops computational techniques to extract interesting information from microscope images of cell cultures.