Cell migration
Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations.
[1] Errors during this process have serious consequences, including intellectual disability, vascular disease, tumor formation and metastasis.
Due to the highly viscous environment (low Reynolds number), cells need to continuously produce forces in order to move.
Such videos (Figure 1) reveal that the leading cell front is very active, with a characteristic behavior of successive contractions and expansions.
The amoeba Dictyostelium discoideum is useful to researchers because they consistently exhibit chemotaxis in response to cyclic AMP; they move more quickly than cultured mammalian cells; and they have a haploid genome that simplifies the process of connecting a particular gene product with its effect on cellular behaviour.
It has been found that microtubules act as "struts" that counteract the contractile forces that are needed for trailing edge retraction during cell movement.
In the case of Dictyostelium amoebae, three conditional temperature sensitive mutants which affect membrane recycling block cell migration at the restrictive (higher) temperature;[22][23][24] they provide additional support for the importance of the endocytic cycle in cell migration.
If they are regarded as cylindrical (which is roughly true whilst chemotaxing), this would require them to recycle the equivalent of one cell surface area each 5 mins, which is approximately what is measured.
Historically, the physicist E. M. Purcell theorized (in 1977) that under conditions of low Reynolds number fluid dynamics, which apply at the cellular scale, rearward surface flow could provide a mechanism for microscopic objects to swim forward.
The migration of supracellular clusters has also been found to be supported by a similar mechanism of rearward surface flow.
[32] It is proposed that microdomains weave the texture of cytoskeleton and their interactions mark the location for formation of new adhesion sites.
Myosin interaction with the actin network then generate membrane retraction/ruffling, retrograde flow, and contractile forces for forward motion.
From biophysical perspective, polarity was explained in terms of a gradient in inner membrane surface charge between front regions and rear edges of the cell.
And where these are located appears in turn to be determined by the chemoattractant signals as these impinge on specific receptors on the cell's outer surface.
[17][39] When present, microtubules retard cell movement when their dynamics are suppressed by drug treatment or by tubulin mutations.
[40][41][32] This approach is based on the idea that behavioral or shape changes of a cell bear information about the underlying mechanisms that generate these changes.
Reading cell motion, namely, understanding the underlying biophysical and mechanochemical processes, is of paramount importance.
