BB23: A new mechanism of motility: the role of the bleb

Background

Damaged skeletal muscle is repaired by stem cells. The first step in this process necessitates the migration of stem cells to the affected region. It has long been thought that cells move by degrading surrounding material and then extending protrusions, called lamellipodia, that pull the cell forward. However, a new mechanism for cell movement has been discovered, which relies on the formation of spherical blisters (blebs) that protrude from the membrane, permitting a cell to squeeze in between surrounding material.

Techniques and Challenges

Initially, we have been concerned with blebbing stem cell movement of a muscle fibre. Assuming that the ‘fine-grain’ structure of the membrane can be decoupled from the movement of the blebs, we are led to model the motion of the cells as a random walk. Although domain geometry is non-standard, we have produced analytical results that can be compared with experiments.

Results

Expressions for position and time on a cylindrical domain have been derived and compared with statistics derived from trajectories provided by our collaborators. Importantly, we are able to classify blebbing cell treatments by their trajectory data. We find that nitric oxide (NO) can rejuvenate not only speed but also directionality, whereas certain other treatments can do only one of these. In effect NO reverses the aging process.

The Future

In addition to considering the macroscopic motion of the blebbing cell populations, we will investigate how the blebs are able to translate into motion. Currently, it is not known how blebs form and stabilise before retracting. We aim to produce a theoretical formalism to test possible mechanisms. Through understanding the blebbing structure, we suggest possible ways of altering their properties that will affect a blebbing cell's motion. We will then extend the framework to consider contraction as well as expansion. Finally, we intend to constrain the cell to move along fibres in order to compare theory with experiment.

References

[12/26] Collins-Hooper H., Woolley T.E., Dyson L., Patel A., Potter P., Baker R.E., Gaffney E.A., Maini P.K., Dash P.R., Patel K.: Age related changes in speed and mechanism of adult skeletal muscle stem cell migration

Otto A., Collins-Hooper H., Patel A., Dash P.R., Patel K.A.: Adult Skeletal Muscle Stem Cell Migration Is Mediated by a Blebbing/Amoeboid Mechanism, Rejuvenation Research 14: 249-260, 2011