Welcome back with another blog. Today, we will explore a topic I guess everyone loves: eating! But hold on to your burger and pizza or your luscious honey garlic chicken that was slightly charred on top of your frying pan that you're about to chow down with your fluffy sticky bowl of rice. We are not talking about those kinds of food or eating, today we're talking about how your cells eat (and drink).
So I assume we are all familiar with how our digestive system work, right? Everybody who learned their biology in highschool is probably too familiar with this process. Your stomach grinds and mixes up your food, and your intestine absorbs all the nutrients and your blood deliver those nutrients to every cell in your body. Even though for the most parts, the cells in your body will take in these nutrient molecules via specific channel proteins on the cell membrane, recent evidence suggests the emergence of an ancient eating process that is being used more often when your cells start becoming cancerous called macropinocytosis! Uh oh, that sounds very scary, doesn't it? And it is! And surprisingly enough, since its first discovery in the 1930s, how macropinocytosis works is not very well understood at all. There are many forms of endocytosis (endo mean going inside, cytosis means the cell), but macropinocytosis is one of those processes that are the least understood. So a better understanding of this will be hugely important!
Ok, so going back to the cancer cells, as you know these cells like to divide. They just want to divide forever, and this process needs a lot of energy. Remember last time when I mentioned how the cells actively trigger your body into deliver food and blood to them? Well, turns out that's not enough. The cancer cells like to eat even more, they literally digest the surrounding matrix (remember extracellular matrix from last time?, yeah that matrix) and then chop it up and eat it. The matrix is basically proteins, and the cells want to eat as much as they can, so they eat the matrix as a source of nutrients to grow. And they do this by macropinocytosis. Even scarier, by eating away these matrix, they can start to metastasise. So what do this process look like? Well, in the lab we can culture the cells and then label the surrounding media with a fluorescent dye. If the cells eat this media, you should be able to see the dye go inside the cell. I stumble across this process while studying my protein of interest. Here is a video I took of a cell eating:
In this video, macropinosomes are the cyan bubble you can see there, and the magenta stuff is the dye that I label the surrouding. So as you can see, this is a melanoma cell, and clearly the dye is being taken inside the cell, in one of those cyan bubbles. The cyan stuff is actually the protein that I have been studying. You can see the protein comes and goes, pretty cool, huh? Nobody knows what this protein does and that is why I am studying it, and hopefully I can contribute a bit of knowledge to the field to better understand this process. However, it's not all bad because afterall, the cancer cells just hijacked something that was basically normal and turned it to their side. Normally though, your immune cells like your macrophages and dendritic cells do alot of this process. Together with a sister process (which perhaps a bit more familiar with many people) called phagocytosis, they sample through your body, cleaning up any dead cells as well as checking for potential infection. Look a bit closer into macropinocytosis, we can actually see many other proteins at work too. Take look at this second video:
In this video, magenta colour is our familiar protein called actin (remember?) and cyan is my protein of interest. You can see that as the cyan bubble comes inside the cells, the cyan signal disappears, and you can see the magenta (actin) signal moving just around the rim of the vesicles. We think that they are actually what pushing the vesicles inside the cell.
All of these videos are taken using what we called confocal microscope. We use this special microscope to see fluorescence. The one that I'm using here is even better because it is a super-resolution one, so the images come out are even better in quality. So why is it matter? Well if you can imagine how tiny proteins are, a better microscope could let us see these tiny speckles much better, like the one you can see above!
So there you go. I hope you find this cell eating/drinking subject interesting. And of course it is vitally important that we understand this process better, because the better our understanding, the better we can come up with a therapy to target this process in pathological conditions like cancer.
Until next time :)
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