Cells have a life of their own. They are like buildings, with a scaffolding that supports mechanical loads. Cells change shape, structurally remodeling themselves. They generate mechanical forces for myriad biological processes. Understanding how these innermost mechanisms work can tell you a lot about physiological and pathological processes, such as cancer metastasis, embryogenesis, neuron growth, and cell migration.
That means getting to know the actin cytoskeleton. Actin is a protein that forms filaments; the cytoskeleton is the network comprised of those filaments. This “polymeric” network within cells — polymers consist of multiple repeated units, and polymeric networks are made of multiple polymers — plays a crucial role in a wide range of cellular functions.
For example, when the actin cytoskeleton behaves as a scaffolding, the mechanical properties of individual filaments and the network structures affect how much and what type of loads the cell can support. When the actin cytoskeleton changes the cell shape via structural remodeling, the dynamic behaviors of actin filaments and actin-associated proteins — actions such as binding, unbinding and turnover — enable the disassembly of existing structures and the reassembly of new ones.
The actin cytoskeleton is of great importance in cancer metastasis. The initial stage of cancer metastasis is called intravasation — the invasion of the cancer cells. During intravasation, cancer cells migrate from an initial tumor site to blood vessels through a dense polymeric extracellular matrix. The actin cytoskeleton plays a major role in this process.
Cells also use the force produced by the actin cytoskeleton to communicate with one another during wound healing and blood vessel formation. The actin cytoskeleton is pivotal in embryogenesis, facilitating the multiple cell divisions during the development of the embryo through a contraction motion. At the later stages of the process, a flat sheet of cells is converted into a hollow, tube-like structure via folding — again, induced by mechanical forces from the actin cytoskeleton.
I developed a model, using the C programming language, to investigate the actin cytoskeleton. Using the Purdue supercomputer and national supercomputing centers for simulation, my model has revealed key mechanistic features of the actin cytoskeleton that current experimental approaches have not been able to illuminate.
In all biomechanical phenomena, the delicate balance between force generation, transmission, and relaxation is very important, and disrupting that balance has dramatic impacts on the pathogenesis of disease. By developing multi-scale computational models, I am currently trying to shed light on the universal roles and underlying principles of force generation, transmission, and relaxation in biological processes at cytoskeleton, cell and tissue scales. Insights into these intrinsic mechanisms can help us find a therapeutic target for treating diseases.
We still need to create more realistic models and simulation techniques to study biological processes without significant loss of information and details. Yet, considering the efforts currently under way in a number of labs, I envision computational models contributing to the treatment of a wide variety of diseases in the very near future.
Taeyoon Kim, Ph.D.
Weldon School of Biomedical Engineering
College of Engineering, Purdue University