Mesenchymal stem cell differentiation influenced by molecular motors

Written by Ebony Torrington

Scientists have altered the differentiation of mesenchymal stem cells into osteoblasts using rotating motors. The team manipulated the protein matrix on which the stem cells are grown using rotating molecular motors, shifting the cells from multipotency.

Researchers from the University of Groningen and the University Medical Center Groningen (Netherlands) have differentiated stem cells into osteoblasts using rotating motors. In order to alter the protein interactions of the cells, the team manipulated the protein matrix on which mesenchymal stem cells (MSCs) are grown, using rotating molecular motors. The results have been published in Science Advances and demonstrated that the MSCs tended to stay multipotent without rotation. This work highlights the fact “the type, amount, conformation, and morphology of adsorbed proteins are affected by the rotary motion” and that this process, can directs cellular behavior and influence the differentiation capabilities of MSCs.

 “Cells are sensitive to the structure of the surface that they attach to,” explained Patrick van Rijn (University of Groningen). “And movement is an important driver in biology, especially continuous movement.”

The team linked molecular motors to a glass surface and coated it with protein. The surface was then either exposed to UV irradiation to power the motor, or not exposed to UV light. Motor movement ceased after approximately one hour and MSCs were seeded onto the protein layer, left to attach and differentiation factors were added. MSCs grown on protein that had been exposed to rotation were more inclined to specialize into osteoblasts compared to cells that had not been rotated, which tended to stay multipotent.

“In our study, we had continuous movement, which is much more in line with the continuous motion found in biological transport and communication systems. The fact that the motors are driven by light is important,” commented Van Rijn. “Light can be carefully controlled in space and time. This would allow us to create complex geometries in the growth matrix, which then result in different properties for the cells.”

The protein layer was observed using atomic force microscopy and simulations of the interaction between the protein and molecular motors. It was found that the movement induced structural changes in the protein matrix.

“The movement of motor molecules interferes with the alpha-helices in the proteins, which causes structural changes,” said Van Rijn.

The way in which the cells attached was affected by the change in the surface structure of the adhered protein. This led to altered cell behavior within the MSCs, such as the affinity for differentiating into osteoblasts. “It’s like a domino effect, where smaller stones consecutively topple slightly larger ones so that a large effect can be achieved with a small trigger,” Van Rijn elucidated.

“Changing the properties of a surface to affect cell fate has been used before,” stated Van Rijn. However, previous studies mostly used switches, consequently the change was from one state to another rather than continuous.

Source: Zhou Q, Chen J, Luan Y, Vainikka P, Unidirectional rotating molecular motors dynamically interact with adsorbed proteins to direct the fate of mesenchymal stem cells. Sci. Adv. 6, 5, eaav2756 (2020);

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