Protein Pattern Hierarchy Encodes Information that Reflects Cell Shape

Biophysicists at Ludwig-Maximilians-Universitaet (LMU) in Munch have developed a new theory, which accounts for the observation that cells can perceive their own shapes, and use this information to direct the distribution of proteins inside the cell. The study—published in Nature Physics—describes how a concentration gradient formed within the cell itself encodes the shape information of the cell and gets decoded by self-organized protein patterns.

Using starfish oocytes as a model system, the research team explained how robust protein patterns can emerge in the face of drastic changes in cell shape. The researchers placed single oocytes in differently shaped microchambers, thus forcing the cells to adopt the geometry imposed by the boundary of each container. "We found that, although the pulse of Rho activation propagates in a correspondingly altered manner in the deformed cells, it always reaches the position at which the nucleus lies," says lead researcher Erwin Frey. "This fascinating observation proves that the Rho pulse recognizes the shape of the cell and adapts to it."

To understand the mechanism behind this adaptability, the team went on to develop a biophysical theory that accounts for this finding. The model is based on the earlier discovery that the cell-cycle regulator Cdk1 is asymmetrically distributed in the oocyte cytoplasm, where it forms a concentration gradient that extends from the nucleus into the cytoplasm and decays with time. This gradient enables the proteins on the membrane to adapt to the cell shape.

"The key insight is that the protein that activates Rho measures the gradient close to the membrane and marks a threshold concentration of the gradient: It forms a front-like concentration profile on the membrane, such that the front is positioned exactly at the threshold concentration. At this front position, the Rho activator, in turn, locally triggers an activity pulse of Rho," the team adds. As the gradient decays, the position of this threshold value moves at varying speed along the membrane, depending on the cell shape. Thus, via this hierarchy of protein concentration profiles, the shape information that is encoded in the gradient gets transformed into a mechanochemical response—the contraction wave that passes over the membrane.