Research article titled Exploring the inhibitory effect of membrane tension on cell polarization was published at Jan. 30th on PLoS Computational Biology. The group of Feng Liu’s Lab and Lei Zhang’s Lab from Center for Quantitative Biology used single-cell experiments and theoretical model to explain the inhibitory effect of membrane tension on polarization. Higher membrane tension improves the stability of cell polarization.
Cell polarization plays an important role in cell division and migration. Experiments show that cell polarization is regulated both by biochemical and mechanical factors, i. e. membrane tension exerts a long-range inhibition. However, models in most of recent studies are only based on reaction-diffusion equations and without taking mechanical factors into consideration.
This study developed a cell polarization model coupling the two factors by virtue of phase field formula, quantitatively depicted the interactions among polarity-related proteins Rac-GTPase, cytoskeletal protein F-actin and cell membrane tension. Meanwhile, research indicated that cancer stem cell (CSC) is more likely to polarize than non-cancer stem cell (NCSC) because of smaller membrane tension. Researchers verify the predictive results through experiments (apply single-cell imaging technics into spontaneous polarization in microfluidic array). Statistics show that CSC is prone to polarize and change the direction of polarization. Another striking result of this study is the first time to recapitulate Houk et al. (Cell, 2012) by running simulations. Their paper reveals that aspiration (elevation of tension) and release (reduction of tension) result in a decrease in and recovery of the activity of Rac-GTP, respectively, and that the relaxation of tension induces new polarity of the cell body when a cell with the pseudopod-neck-body morphology is severed.
The framework of model in this research may be naturally extended to explore mechanical effects on other complex biological behaviors, such as cell migration and cell fate decision. On the other hand, research reveals the characteristics of cancer stem cell metastasis. This is promising for designing anti-cancer (based on mechanical regulation) drugs in the future.
Dr. Weikang Wang (Ph. D from School of Physics, Peking Univ., Postdoc in Pittsburg Univ.) and third-year Ph. D Candidate Kuan Tao (from Center for Quantitative Biology, Peking Univ.) contributed equally to this work. Dr. Feng Liu and Dr. Lei Zhang are corresponding authors. This work was supported by the National Natural Science Foundation of China.