Smooth Moves

Summer 2014

Sean Sun (left) and Konstantinos Konstantopoulos

Human cells are remarkable machines. They convert nutrients into energy, build our tissues and organs—and, according to the Whiting School’s Sean Sun and Kostantinos Konstantopoulos—may well have been the original hybrid vehicles.

In a paper recently published in the journal Cell, Sun, an associate professor of mechanical engineering, and Konstantopoulos, professor and chair of the Department of Chemical and Biomolecular Engineering, described a previously unknown means of cellular locomotion.

The textbook explanation of how cells get around involves the same proteins, actin and myosin, that make muscles contract: Actin filaments at the leading edge of a cell extend forward while myosin causes the trailing edge to retract, allowing the cell to crawl along a flat surface like a microscopic inchworm. (Proteins called integrins permit the cell to adhere to the surface in the first place.)

In 2012, however, Konstantopoulos demonstrated that when the function of actin, myosin, and integrin was disrupted, cells were still able to move through the kinds of narrow, three-dimensional longitudinal channels that are found throughout the human body. The question was, how did those cells manage to keep moving with sugar in their tanks? The answer could have far-reaching implications. Cell migration plays a crucial role in many pathological conditions, including cancer, so understanding how cells move, and how they can be stopped, could lead to new therapies.

Sun suspected that the solution might lie in how cells regulate the flow of water across their membranes. In their Cell paper, the two present a mathematical model, confirmed by experiments on different tumor cell lines, which describes how cells move through narrow microchannels by doing precisely that. (Hongyuan Jiang, in the Sun lab, and Kimberly Stroka, in the Konstantopoulos lab, also made important contributions to the work.)

When a cell is placed at one end of a narrow channel and a chemical attractant is placed at the other, a variety of specialized proteins arrange themselves on the cell’s membrane to let water and ions flow in through the front and out through the rear, propelling the cell forward. The researchers could even cause the cells to change speed and reverse course by altering the concentrations of ions on either side of them—just as the model predicted.

By discovering an alternative to the conventional model of cellular movement, Sun and Konstantopoulos have revealed cells’ ability to shift gears depending on the terrain they face—potentially uncovering a new class of targets for drug development.  Sun, Konstantopoulos and Stroka collaborated via the Johns Hopkins Institute for NanoBioTechnology and Physical Sciences-Oncology Center.

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