The key to fighting cancer: be flexible

In my previous post on soft nanoparticles, you were introduced to polymer-based nanoparticles that could be used in biomedical applications, one of which is cancer therapy. These nanoparticles have a range of useful properties for cancer treatments, including their spherical shape and small size (~100 nm), both of which are similar to exosomes, small globules that are used in nature for transferring proteins between cells. Since cells naturally absorb exosomes, artificial particles with this size and shape should also be easy for cells to absorb, which means these particles could be used to deliver drugs into cells. While this idea sounds promising, it hasn’t worked out in practice --  when drug-loaded polymer-based nanoparticles were injected into a tumor, subsequent tests showed that less than 1% of the injected dose entered the cancer cells. Since these particles were the correct size and shape, why didn’t they get inside the target cells?

The Peter Parker cell

Berginski M, Vitriol E, Hahn K, Gomez S [CC BY 2.5 (https://creativecommons.org/licenses/by/2.5)], via Wikimedia Commons

“USE YOUR LEGS!” That’s what might have been yelled at you the first time you went climbing. We are so used to walking or running that we don’t even think about how we do it. But when we face a new environment, such as a steep slope, we realize that finding the best strategy to move through space is not so easy. Now, imagine you are as small as few dozens of microns, without legs or arms, and you live in a viscous fluid. How would you move? This is the question biologists who are interested in cell movements have been trying to solve. By observing cells under a microscope, they saw that depending on their type or their environment, cells exhibit a wide variety of motion strategies. However, one thing never changes: cells need to exert forces on their environment to move. To do so, some kinds of cells create structures called focal adhesions. These structures are made up of several proteins, assembled on the outside of the cell. Like tiny bits of double-sided tape, their purpose is to stick the cell to whatever is nearby (see Figure 1). In slightly more technical language, focal adhesions connect the molecular skeleton of the cell to a substrate.

Sticky bees: How honeybee colonies stay safe outside their hives.

A honeybee colony can only exist when many individual bees cooperate. When a hive becomes too crowded, about 10,000 of the workers and a queen leave the hive to form their own colony. While the scout bees are searching for a new nest site, the rest of the bees are exposed to all of the dangers of the outside world, such as predators and storms, and have to stick together for protection. They form a “cluster”, which hangs on a nearby tree branch (as in Figure 1a) until a new suitable nest site is found. Sometimes, beekeepers hang these clusters from their faces as a “bee beard”.

Fold and Unfold

Animation of GFP unfolding

For the most part of biology, it is form that follows function. Proteins are a perfect example of this -- they are made of a sequence of amino acids (the protein building units), which are synthesized by the ribosome. Once synthesized, the long strings of amino acids fold up into a particular 3D shape or conformational state. Proteins take less than a thousandth of a second to attain their preferred conformational state (called “native state”) that -- if nothing goes wrong -- ends up being the same for a given sequence. This process is called protein folding. Explaining how a protein finds its folding preference out of all possible ways in such a short time is a longstanding problem in biology.

Illuminating tiny structures: An introduction to small-angle scattering

Bellevue Beach in Klampenborg, Copenhagen, Denmark.

We are surrounded by phenomena caused by the scattering of light. When enjoying a sunny day at the seaside, like in the photo at the top, why is the sky blue? Blue light scatters more than red light. Why is milk opaque? Protein and fat particles scatter light. If you are reading this with blue eyes, your eye color is due to light scattering. Scientists use the same general scattering principle to study the structure of soft materials using the scattering of well-defined radiation. Scattering measurements reveal structures between an ångström and hundreds of nanometers, an important region for studying soft matter. Just as the color of the sky results from light scattered by air molecules, the scattering of X-rays and neutrons tells us about the size and shape of compounds in soft materials along with their interactions, and I will focus on these two types of radiation.

What is soft matter?

Keiser et al. & Lutetium Project

Look inside a glass of milk. Still, smooth, and white. Now put a drop of that milk under a microscope. See? It’s not so smooth anymore. Fat globules and proteins dance around in random paths surrounded by water. Their dance—a type of movement called Brownian motion—is caused by collisions with water molecules that move around due to the thermal energy. This mixture of dancing particles in water is called a colloid.

Making Biomolecular Crystals Soft and Self-healing — Just Add Polymer

In the world of engineering, crafting a material that meets the needs of your application is challenging. Often, a given material may only provide a handful of the required properties for that application. Instead, you may choose to combine two or more materials, forming a composite with all of your desired properties. In this week’s paper, Zhang and coworkers from the University of California at San Diego took a similar approach in the world of biology by combining a biomolecular crystal with a flexible polymer. The crystal provides structure to the composite and the polymer contributes to its flexibility and expandability. They showed that the composite could reversibly expand to nearly 570% of its original volume and unexpectedly found that it was self-healing.

Using sound to build a wall: how physicists measure pressure in active systems

You know how sometimes you tell to yourself things like “life is complicated”? Theoretical physicists are constantly reminded of this fact when studying living organisms. Recently, a new field of physics has emerged, inspired by the observation of living systems. What forces do cells exert during metastasis in cancer? What are the growth dynamics of biofilms of bacteria? How can a school of fish organize itself and move simultaneously? These are questions raised in the physics of active matter. Active matter is an assembly of objects able to move freely and capable of organizing into complex structures by consuming energy from their environment. Active matter can be composed of living or artificial self-propelled particles.

Tiny Tubes Racing in a Donut-Shaped Track

The shape of a container can affect the flow of the fluid inside it. Water in a narrow stream flows smoothly, but once the water molecules make their way into a pond, they spread out and no longer flow coherently. If you blow into a long, narrow straw, the air will go straight through. Once the air flows into the large room you are standing in, it slows down as it mixes with the air around it, so someone standing five feet away from you won’t feel a breeze at all.

The above examples show how the shape of a container affect the flow of passive fluids. In today’s study, Kun-Ta Wu and colleagues investigated how the motion of active fluids, fluids that flow using an internal source of energy, is also affected by the shape of their container. They used a system of microtubules, chains of proteins assembled into long, stiff rods. Clusters of a protein called kinesin exert a force on microtubules by “walking” along them. Microtubules interact with each other to form swarms or turbulent-like flows.