A team of Rice University researchers have developed a theoretical approach to analyze the process by which protein building blocks form the biopolymer skeletons of living cells.
The cytoskeleton, made of fibers and microtubules, gives a cell its shape and provides the “roads” along which proteins and other cargoes travel. It changes constantly over the cell’s lifetime as the fibers and tubules are chemically pulled apart into subunits called monomers that reconnect in other locations within the cell.
[Photo caption: Rice University theoretical biophysicist Anatoly Kolomeisky, left, and postdoctoral researcher Xin Li analyzed the mechanics behind cellular structures that constantly change. Their theory on cytoskeleton proteins could help chemists and bioscientists view these processes in finer detail. Photo credit: Jeff Fitlow]
The work by theoretical biophysicist Anatoly Kolomeisky of the Department of Chemistry and Center for Theoretical Biological Physics at Rice University in Houston and postdoctoral researcher Xin Li seeks to quantify the chemical basis for those changes through a formula that could be of great value to bioengineers and drug companies. They detail their approach in a new paper published in the American Chemical Society’s Journal of Physical Chemistry. titled “A New Theoretical Approach to Analyze Complex Processes in Cytoskeleton Proteins” (J. Phys. Chem. B, Article ASAP DOI: 10.1021/jp500268q, Publication Date (Web): February 26, 2014)
In the article abstract, Drs. Li and Kolomeisky explain that cytoskeleton proteins are dynamic biopolymer filament structures that support a large number of important biological processes, and exist in nonequilibrium conditions stimulated by hydrolysis chemical reactions in their monomers. They note that current theoretical methods provide a comprehensive overview of biochemical and biophysical processes in cytoskeleton proteins, but observe that the description is only qualitative under biologically relevant conditions, because the theoretical mean-field models utilized neglect correlations.
Their research has led to development of a new theoretical method to describe dynamic processes in cytoskeleton proteins that takes into account spatial correlations in the chemical composition of these biopolymers. Li and Kolomeisky’s approach is based on analysis of probabilities of different clusters of subunits, and allows them to obtain exact analytical expressions for a variety of dynamic properties of cytoskeleton filaments. By comparing theoretical predictions with Monte Carlo computer simulations, they have demonstrated that their method provides a fully quantitative description of complex dynamic phenomena in cytoskeleton proteins under all conditions.
Dr. Kolomeisky’s research group is focused on the area of statistical mechanics of complex systems and theoretical biophysics using analytical and computational tools. He expects his formula, when combined with experimentation, will reveal more detail than ever about what triggers proteins in cytoskeletal components like actin filaments and microtubules to combine, come apart and recombine.
“These proteins are important because they essentially support all the processes within cells,” says Dr. Kolomeisky in a Rice release. “Experimentalists are beginning to have a good understanding of how cytoskeletal filaments assemble. As theoretical people, we build computational models, caricatures of real phenomenon that we use to analyze the energetic relationships at the molecular level.”
Comparing cells to cities, Dr. Kolomeisky notes: “Big cities can’t survive without good roads so people can travel from one part to another, and it’s the same here: The microtubules and actin filament are used as highways. A growing city can build new roads, but a cell is closed and has a limited amount of building material, so it breaks microtubule polymers down into monomers and redeploys them to build roads in other places. This is known as dynamic instability.”
“It’s economical,” he continues, “because the cell doesn’t have to bring in new material, and to make material costs energy. So a cell can break down a highway where it’s not needed and build a new one from this material.”
[Graphic caption: A schematic of a one-dimensional biopolymer illustrates the formula by Rice University researchers to predict how monomers attach to or release from the fibers and microtubules that make up a cell’s skeleton. Graphic credit: Xin Li]
The nanoscale polymers are one-dimensional – that is, simple chains of molecules – that wrap around each other to form filaments and tubules. “It’s known that for one-dimensional objects, correlations should be important, and we found that is true for these proteins,” Dr. Kolomeisky explains. “We found a simple mathematical way to take these correlations into account.”
The Rice researchers believe that when monomers bind to the polymer chains, hydrolysis – a chemical reaction in the presence of water molecules – changes the properties of the polymer. “Essentially, each monomer can have two states: hydrolyzed or non-hydrolyzed,” says Dr. Kolomeisky. “Non-hydrolyzed molecules act as caps that keep the proteins stable, while hydrolyzed molecules allow the proteins to break apart. “We’re able to describe the properties of these polymers in experimentally measurable rates of attachment, detachment and hydrolysis.”
Dr. Kolomeisky further notes that the research should be useful to cancer researchers. “One of the main methods of fighting cancer is through Taxol or other compounds that bind to microtubules. They stop the process of dynamic instability, and the cell dies,” he says. “We hope our formula will help understand the process on a more physical, chemical level.”
The Welch Foundation supported the research.