Using elastic sheets, it is difficult to exclude the Poisson's effect completely. In the case of our new device, when the sheet was stretched, 1/4 of perpendicular shrinkage took place, simultaneously. Cells showed random migration under the cyclic stretching stimuli of 10% stretching ratio and 10-s time cycle (Figure 3, A, B, and I). This indicates that cyclic stretching of <10% does not affect directionality of cell migration. In all experiments, the ratios of perpendicular shrinkage by Poisson's effect were <7.5% (Table 1). Thus, the perpendicular shrinkage in all experiments should not affect the directionality of cell migration. On the other hand, the speed of cell migration increased even when the ratio of cyclic stretching was 10% (Figure 3J). These results suggest that the perpendicular migration and increase in the migration speed in response to the cyclic stretching stimuli are mediated by different mechanisms.
The mechanical interaction between the cell and substratum may act as a primitive signaling cascade for determining polarity and migration direction because cells can migrate even if there are no additional environmental signals (such as a concentration gradient of a chemoattractant). It is generally believed that the mechanism of cell migration is based on actin polymerization at the front of the migrating cells, and actomyosin-dependent contraction at the rear (30). We proposed a model for cell migration in which myosin II may accumulate and exert an active force at the stretched region of the cell (31). The aspiration of a small part of the cell surface by a micropipette induced myosin II accumulation at the tip of the aspirated cell lobe, suggesting that myosin II may accumulate in response to mechanical stimulation (5). Our hypothesis of the mechanism of the migration perpendicular to the cyclic stretching is as follows: In response to the right-left cyclic stretching of the substratum, myosin II may accumulate right-left symmetrically. This may make the probabilities of the right and left migration equiprobable. A future topic of interest is determining whether the stretch stimuli generate polarized cell migration via polarized regulation of actin polymerization or actomyosin-dependent contraction. Further detailed observations using the new device described here will shed light on the relationship between the mechanosensing and molecular machinery involved in cell migration.
We thank Peter N. Devreotes (Johns Hopkins University, Baltimore, MD, USA) for the kind gift of the Dictyostelium cell line RI9. This study was partly supported by a Grant-in-Aid for Scientific Research on Priority Areas to SY from Japan's Ministry of Education, Culture, Sports, Science and Technology (MEXT). We are grateful for their support.
The authors declare no competing interests.
Correspondence Address correspondence to Yoshiaki Iwadate, Department of Functional Molecular Biology, Graduate School of Medicine, Yamaguchi University, Yamaguchi 753-8512, Japan. Email: [email protected]References
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