Fueling Cell Movement

One cancer line Sun and his team studies is MDA-MB231 (shown above), a metastatic breast cancer cell that is highly aggressive with limited treatment options for patients.

Cars require fuel, or energy, to move and get people from one destination to another. How much fuel the car will need though depends on many factors. Cars consume fuel based on their engine and body design, but the environment outside of the car also influences fuel consumption, like terrain, wind, temperature, and road conditions.

Like cars, cells need to metabolize energy to move. How a cell metabolizes its fuel, adenosine triphosphate, is determined by environmental factors outside of the cell. But how much energy a cell consumes to generate movement has never been studied in detail because measuring the metabolic activity of a single cell is extremely difficult. “Nobody buys a car by just looking under the hood—you buy it by the overall specs of the car like size, mpg (miles per gallon), etc. And when we look around there is very little measurement of performance factors like mpg for cells,” said Sean Sun, INBT core faculty member and professor of mechanical engineering.

While cells are not mechanical machines, they share similar characteristics and can exhibit machine-like behavior. Knowing what a cell needs to generate forces and perform mechanical functions can help researchers understand cell movement.

“A lot of biological research is like taking a car apart, naming the parts, and deciphering what each part does,” said Sun. So rather than study

the activity as individual parts inside a cell, Sun and his colleagues want to know what determines the overall “mpg” of cell movement, and Sun’s goal is to utilize new information about cell metabolic activity to further understand cancer physics, specifically, metastasis. His research can assist in locating weak points in “...when we look around there is very little measurement of performance factors like mpg for cells.”

what external factors influence energy requirements for cell movement using the framework of energy balance and computational modeling.

Cells move using different motility mechanisms depending on their environment. Sun’s team looked at two movement mechanisms— actin-driven and water-driven. In actin-driven movements, cells move similar to an inchworm by anchoring themselves to surrounding surfaces to push themselves forward. In water-driven movements (also called osmotic engine) cells move like jet engines, by pulling fluid in and expelling fluid out behind it to move forward.

Each movement was analyzed in different fluid environments, characterized by the hydraulic resistance of the environment. Hydraulic resistance depends on viscosity and geometry of the microenvironment. Viscosity relates to the “thickness” of the environment. For example, it is harder to move through honey than water.

They found that actin-driven movement is inefficient in high hydraulic resistant environments because more energy is required, whereas water-driven movements become more efficient. It seems the best strategy for cell movement using the least amount of energy depends on the cell’s external environment. Cell movement energy efficiency is also determined by their cell shape and their membrane’s water permeability. cancer cells and their processes, which could potentially lead to better treatment methods for patients.

The next step is to experimentally measure cell metabolic activity with his colleague Konstantinos Konstantopoulos, INBT core faculty member and chemical and biomolecular engineering professor. Konstantopoulos also studies cancer metastasis and their physical environments using microfluidic devices that mimic cancer cell’s microenvironment.

“Designing and conducting experiments can take a long time, and this is where theoretical modeling and mathematics can help by offering new directions to explore and study biological processes, physiology, development, and so forth. It can help us determine if we are going in the right, or wrong, direction,” said Sun.