Cellular and Molecular Mechanics

Cellular and Molecular Mechanics I was invited by Dr. Zhigang Suo to write a short piece on “Cellular and Molecular Mechanics”. I am writing this informally to introduce this subject matter rather than talk in vernacular such as mechanotransduction, phosphorylation, etc. I have more formal papers if someone is interested in more detailed discussions on this subject area. This is a field in which I have been working for over a decade now and I find it more exciting every day. The question always is how does mechanics affect biological processes. This is a very interdisciplinary subject matter as mechanists, engineers, physicists, chemists, and biologists have been investigating this process from various perspectives. I am obviously not the first to study this process. For most of us, it is realized from an empirical perspective that mechanics matters to biology, but exactly how mechanics specifically alters biochemistry continues to be highly debated today. Mechanics of course matters in many physiological areas. Your blood flows, your heart pumps, your bone and muscle feel mechanics. Not only does the body experience mechanical stimulation, but it reacts biochemically to it. A wonderful example is when people go into space (NASA) for long periods of time. The bone in one’s body begins to resorb in a similar response mode to what one experiences in aging (osteoporosis). This is primarily due to just the change in the gravity (mechanics). Other diseases are related to these issues including the two biggest killers: heart disease and cancer. While biomechanics on this scale has been studied for awhile (Leonardo Da Vinci, who was interested in mechanics, also wrote one of the first texts on anatomy), the movement to the cellular and molecular scales has brought a tremendous amount of excitement. I consider the cell as one of the ultimate smart materials exhibiting these characteristics. The cell has evolved over millions of years and is designed better than almost any system that we can personally build. Just as the biological eye provides a beautiful template for optics based lenses, much can be learned about building technology (“nanotechnology” and “microtechnology”) through examining the behavior of cells and molecules.

The cell has an amazing structure called the cytoskeleton (“cyto” from cytoplasm within the cell and “skeleton” like our body’s skeleton), which can be thought of like a truss structure. At least this is the way that I imagined it when I first started studying this subject. The interesting part is that many years later, I still think of it this way except it has thousands of elements and they can disappear and reappear at any given time (these structural elements are actually biopolymers that can depolymerize and repolymerize constantly). I describe it like this: if I take a building and remove the walls, the ceilings, and the floors out of the building, does the building collapse? No, because the structural supports such as I-beams continue to give it mechanical support. If I take a cell and remove the cell membrane, the cell does not structurally collapse either (as a note, many of us were basically taught in high school that a cell has a membrane and a nucleus as the structural elements). This structure is fascinating as the elements (actin filaments, microtubules, and intermediate filaments) are each optimized for their response. For example, if I was building a vehicle to send into space and I wanted to incorporate an element that resists compression, how would I design it? I would likely use a hollow tube. The amazing part is that the microtubules, which are known to be compressive elements, are hollow tubes….that are around 25 nanometers in diameter! And no person said: let’s build it this way! This is only one example of these interesting structural elements.

While the cytoskeleton provides structural support, it also provides organization. This should not surprise any of us as a cell, which has billions of molecules yet is only tens of micrometers in diameter, must have an amazing organization structure to accomplish all of its complex tasks. I feel that the cytoskeleton in this context is similar to a transportation highway system as it provides the mechanism for transport to move cargo. For example, there are motor molecules within a cell such as kinesin, dynein, and myosin, which move along these cytoskeletal elements and can carry molecules, vesicles, etc. along with them. These motors are highly efficient mechanics based machines that are driven by a biochemical reaction. The efficiency of the motors has been calculated to be up to 50% and if you scale the size of these motors to the size of a car, these motor molecules would travel up to 1000 miles/hour (they travel up to 60 um/sec on their size scale). Furthermore, this movement along the cytoskeleton is like a roller coaster within a cell where the cytoskeleton is the track and the motor molecules are the carts. The cytoskeleton also has the ability to help with the efficiency of accomplishing processes through being an anchoring point (or the cell scaffolding) within the cell. This is somewhat similar to the improvements that the assembly line made for automobile production. Just as the assembly line created a line along which processes where sequentially accomplished at specific stations in a highly efficient manner, many molecules that have specific functions attach to this cytoskeleton and thus have spatial organization when modifying molecules in a sequential and efficient process. This is contrasted with solely a random distribution of molecules reacting with each other through just diffusion within a cell based on solely aqueous characteristics.

These are only a few examples of the amazing mechanics and associated structures that exist within a living cell. Understanding this can not only help address disease-based questions, but can also be leveraged to potentially produce devices and technologies at extremely small size scales. I believe that this continues to be an area where individuals from a mechanics perspective can provide tremendous insight into a fascinating and evolving area that is being pursued by individuals in a diversity of arenas. Please feel free to contact me about this.