The molecules we eat

Transcript

Some of the nastiest cancers are made of cells that are more deformable, or softer, than normal cells. These deadly cancers can migrate through the body and invade other tissues. And the texture of their cells might be telling you more than you might think.

And by making you eat Jell-O, I’m going to tell you more about this exciting field in cancer research. But first, to get you started thinking about the molecules of food, you can open your small tasting bags and remove a small piece of chocolate.

It turns out that getting people to think about food and the molecules that we eat can be an effective way to communicate my scientific research. And it can also be a great way to engage you in thinking and engaging you in the wonderment and curiosity that drives me as a biophysicist to ask questions about the texture of soft materials around me.

So as you’re enjoying this can — this, this chocolate, which is a diversion from cancer, I realize — but it will encourage you to think more about these particular molecules of chocolate and how they give rise to the particular physical properties: its color, its flavor, and importantly its texture.

I began my experiments with molecules as a small child by baking. Here’s a page from my lab notebook. I created recipes, I varied ingredients and their proportions, and I investigated the resulting effects on the texture of baked goods such as cakes and muffins.

Later on in grade school, I started getting more curious about materials, asking why does a rubber band stretch and then contract back to its original configuration? As a graduate student, I learned with even more fascination that some of the individual cells in our bodies can behave very much like little rubber bands.

A beautiful example is that of a red blood cell. There are trillions of these cells coursing through your veins and arteries and squeezing through capillaries which are much smaller than the individual cells themselves.

Like me, you might start to wonder: how does the cell do that? Well, over the past decades, researchers have determined that the molecular makeup of these cells is very finely tuned to achieve a specific shape and deformability. Today, I’m going to tell you about two major types of molecules that are responsible for these physical properties: fats and proteins.

Each cell is surrounded by a membrane. This is a very, very thin nanoscopic sheet of fat. It’s about 1000 times thinner than a piece of Saran Wrap. And the molecules that make up these membranes are, in fact, very similar to the molecules that gave rise to the texture of that piece of chocolate that you just enjoyed. So the next time you go to eat a chocolate bar, you can appreciate cocoa butter and lecithin.

But in cells, these molecules form these sheets of fat, which provide a physical boundary around the cell. It may also provide important platforms that help cells to communicate with other cells.

But fats are not the only molecules that are important for cell shape and texture. Proteins are critical. Proteins, of course, are essential for many biochemical reactions inside of cells, and you may well know them because it’s recommended that you eat about 50 grams of them on a daily basis.

But in addition to their biochemical and nutritional importance, proteins are also essential for structure and mechanics. Bakers well know the importance of gluten. You can think of these networks of proteins as adjoined masses of teeny tiny springs or rubber bands that can each stretch and contract back to their original shape and are essential for the texture and mechanical properties of bread doughs and baked goods.

Inside cells, proteins have similar structural and functional roles, such as shown here in this protein network or scaffold which underlies one of these sheets of fat, much like a tarp would overlay the frame of a tent.

Encapsulated inside of these structures is the genetic material and biochemical reactions that is essential for life, and the topic of much intense research. But cells are also materials, and the research in my lab is driven by wanting to understand the texture of cells.

Why do we think this is important? Well one obvious reason is that the texture and material properties of cells and tissues is critical for physiology. Your bones resist mechanical stress and any contortionist or yogi well knows that your skin needs to stretch and expand. And as we’ve seen, your blood cells need to deform through very narrow capillaries.

But let me tell you about another reason why I think that the texture of cells is important. It turns out that the deformability of an individual cell can be a hallmark of its state of health or disease. For example, red blood cells become stiffer when infected by malaria, and also in sickle cell disease. Interestingly, results emerging from my lab as well as others in our global research community are showing that more invasive cancer cells are more deformable, or softer, than normal cells.

You might start to wonder, “Well, how is it that we measure the texture of cells?” These are experiments you have been doing your whole life. Now I’m going to call on those skills.

So inside of your tasting bags you have two samples of Jell-Os which you can now take out and begin to inspect, observe them, feel them. You can even eat them, they’re food-safe, food grade.

And as you’re observing them, how would you describe their texture? Well common words that one might use are adjectives such as “soft,” “squishy,” “stiff.” But there can also be value in assigning a number to a physical characteristic.

After all, when you go to the doctor’s, they record a number for your weight. They just don’t use adjectives like fat or thin. Especially for scientists, it’s important for us to develop quantitative descriptions so that we can better categorize and compare materials.

So when we’re talking about texture, we use a number that we call the elastic modulus. This is a number, the larger it is, the stiffer or less deformable a material is.

So this is an experiment that we can do in our lab to measure elastic modulus, you can actually do at home in your kitchen. It’s very simple. You simply apply a force and you measure the resultant deformation. You can do this for your Jell-O cube, you can also do this analogously for a spring or an elastic band to sense its stiffness.

So researchers have done this for different types of cells and tissues and can categorize and compare the relative elastic moduli of different tissues. So you can see that skeletal muscle, for example, and muscle cells have a modulus that’s about 1000 times larger than softer tissues such as lung and brain.

You can also play this game for some of your favorite foods to eat and can begin to see that almond and carrot have a much larger modulus than softer foods such as steak, which is even tougher than foie gras.

But I want to come back to cancer. Researchers are finding that malignant or cancerous cells are about two- to four-fold softer than normal cells. And to give you a tactile sense of this difference in moduli, we carefully tuned the elastic moduli of those Jell-O cubes that you just ate so that they match the difference in elastic moduli between a normal and a cancerous cell.

You might be wondering why it is. What is the mechanism behind why these cells get softer? Now that is a complicated question, and we can start with our simpler model system: our Jell-O. And the answer to this question — why, what makes that one jelly cube softer than the other — is simpler. We simply added less gelatin.

Gelatin is a protein. It forms networks very similar to the networks of proteins that are formed inside of your individual cells. And it turns out that the softer network contained fewer proteins, so the structure is looser compared to the stiffer Jell-O cube.

There’s actually an elegant equation that can describe this relationship. And I’ve distilled that down for you here. What you need to understand is that the protein density, how many proteins are in this network, can also be described as the distance between the nodes in that network. So fewer proteins means a larger distance between nodes. So this relationship here is our way of saying that the larger the distance between the, the nodes “l,” the smaller the elastic modulus, the softer the job.

So this simple picture helps to explain why it is that bakers might use a high-protein-content flour to achieve a baked good with a denser texture, such as a bagel. As far as cancer cells go, the story is a little bit more complicated, but we know that alterations in this network of proteins inside of cells helps to explain the softer characteristics of those cells.

So you’ve determined already that being able to squeeze a soft material can be a great way to probe its mechanical properties. But how do we do this for a single cell? The cell is much, much smaller than that Jell-O cube. Even if you scaled down your finger so that it was the size of a human hair, it would still be too large.

So to address this mismatch in scale we are developing in my lab micron scale methods to squeeze and poke individual cells. Let me tell you a bit about how those work.

Well one method is very similar to drinking bubble tea. Some of you may enjoy drinking boba where you suck through a straw deformable tapioca spheres. Now, if you scale down your boba by about 1000 times, you’ve got this method that’s very similar to what we’re developing in my lab.

Some of you who may be visiting the labs later this afternoon may also see a new emerging technology that we recently invented, the ultrafast cell poker. And using this apparatus, we’ve been able to poke cells very quickly and obtain quantitative measurements of their elastic moduli.

Now this should be able to obtain measurements at about 100 times faster or even more rates compared to existing methods that run at about one cell per minute. And considering that tumors consist of millions of cancer cells, this is a significant advance.

Now let’s bring this all back to cancer. Cancer cells spread through your body. And in this process, they have to deform. They leave the initial sight of the tumor, they squeeze through very narrow gaps, perhaps into the bloodstream, and thereafter they can infiltrate into very dense tissue, where they might start to then grow and divide and form more tumors.

Now this process, known as metastasis, is very complicated. But you can begin to see how the deformability of individual cells can play an important role. And we think that by probing the texture of individual cells, this could provide more information into the type of cancer and even potential treatments that may alter the deformability of cells and help to prevent the spread of disease.

So here’s an example of how one of our experiments works. We take ovarian cancer cells, we suck them through these tiny gaps similar to how you would deform your boba or tapioca ball through a straw. The whole time we do this, we’re taking pictures very, very quickly so that we can produce movies that are about 10 times faster than normal video frame rate.

From these movies, we can analyze the amount of time it takes each individual cell to squeeze through a tiny gap. It turns out that the softer cells can deform through more quickly than stiffer cells. Using this method, we’re finding some interesting results. Now I’m going to tell you about two examples.

First, we’re finding that cells from more invasive tumors can actually squeeze through those gaps more quickly. They’re more deformable. Now, this is interesting because it’s suggesting that we might be able to probe the texture of individual cells and this could tell us about the behavior of an entire tumor. And because we can do this so quickly, there’s potential for this to be a prognostic tool that your doctor may use to evaluate cancer in a clinical setting.

Secondly, we find that if we treat these cancer cells with molecules that slow down their growth, that have anti-cancer effects, that we actually see these cells get stiffer or less deformable. And these results have exciting potential because they are telling us that we could possibly search for effective anti-cancer chemotherapy agents simply by probing the inherent texture of cells. Ultimately, this could provide a faster, less expensive method that could complement existing ways to evaluate cancer cells.

Now you still may be asking, well, why do cancer cells have these altered characteristics? And this is a question we continue to work towards that is a hot topic of research. We have some clues. We know that there’s this altered structure in the network of proteins inside of these cancer cells. We also know that by changing expression levels or density of proteins that this can alter, also alter and impact cell deformability. But ultimately understanding more about this, the link between the molecular composition of cells and the impact on their texture, will provide deeper insight into human health and disease.

Here I’ve told you about my passion for cells as materials using the molecules of food. And over the past years I’ve also discovered that food can be an effective vehicle for communicating science. I’d been experimenting this, with this in classrooms full of undergraduate students as well as auditoriums full of general audiences.

Many of the common foods that we eat, such as chocolate, Jell-O, and bread, are things you have vast experience sensing the texture of. So I hope that this has helped you develop a deeper appreciation for both the foods that we eat as well as this exciting frontier in cancer research. Who would have thought that you could learn more about cancer by eating Jell-O?

So the next time you eat, you can remember that texture may be telling you more than you think. Thank you.