Background

The movement of cells is a process required for an organism’s health, whether it be through repairing wounds or by ensuring the correct development of various systems. One specific type of cell, called neural crest cells, are particularly important for their role in forming the peripheral nervous system. However, the mechanisms underlying cell migration are not fully understood. Cell migration is usually manipulated and observed in isolated systems (i.e., cultured flasks), which may not accurately replicate the environment of the cell, meaning that there could be minute differences in the way cells migrate (Gonçalves & Garcia-Aznar, 2021).

There are two main theories that may explain the molecular mechanisms underlying cell migration: the membrane flow model and the cytoskeleton model (Tanaka et al., 2017).  The membrane flow model suggests that cells move by recycling the membrane from the leading edge (the front of the cell when it migrates). This is carried out by endocytosis, a process where substances are moved into a cell by having the membrane pinch inward and encapsulate a substance. The second theory, cytoskeleton model, suggests that the treadmilling of actin is the main force responsible for pushing the cell forward by applying pressure to the leading edge of the cell (Craig,Van Goor, Forscher, & Mogilner, 2012). Actin is one component of the cytoskeleton, a type of scaffold that helps maintain a cell’s shape, as well as aid in functions such as migration and division. 

Methods

Neural crest cell migration was observed by removing a section of tissue from fertilized chicken eggs that had been incubated until the chick had reached a certain developmental age. The chicken eggs were treated with a plasmid, a small piece of DNA that can be used to produce many copies of itself, which helped certain components within the cell fluoresce when excited with a specific wavelength of light. The samples were imaged for a period of 12 hours, with images taken every 2 minutes when testing for the membrane flow model, and every 5 seconds to test for the cytoskeleton model. Data was then transferred to a program for tracking and analysis. 

To test for membrane flow model, the researchers examined changes in total cell volume. While there were changes in the surface area of the cells, they occurred in opposing directions, negating any overall change. Additionally, instead of retrograde membrane motion (movement of the membrane in the opposite direction of the cell’s movement) on both sides of the cell, the membrane exhibited a circular motion. The cytoskeleton model was tested by visualizing the membrane as well as components of the cytoskeleton, such as F-actin (Jung, Kim & Mun, 2020). Data showed that F-actin is moved along the cell through vesicles that are part of the membrane fluid model, suggesting that both models are necessary to explain migration dynamics. 

Discussion

These results support the idea that parts of both models are necessary to explain the process of cellular migration. As cells migrate, they extend finger like structures called lamellipodia, which “sense” the environment ahead of the cell to see where the main body can move. According to the new model, the membrane on the apical side (facing the external environment) migrating toward the back of the cell and the membrane in contact with the surface (basal), moving toward the front of the cell (Li et al., 2020). During this movement, small parts of the membrane are moved into the cell through a different form of macropinocytosis, a form of endocytosis, where nonspecific items in the cellular environment are internalized (Lin, Mintern, & Gleeson, 2020). Contrarily, F-actin is moved toward the lamellipodia by these vesicles, suggesting the dependence of these two models on one another for proper functioning. Additionally, a type of actin called cortical actin lines the edges of the cell, restricts the cell from protruding. This means that even if there are vesicles fusing with the membrane, only areas with no cortical actin, such as the lamellipodia, will exhibit changes in their structure. 

Having an accurate model that explains the components underlying cell migration is necessary because it offers specific targets for future treatments for diseases resulting from defects in migration. Some examples of diseases caused by defects in neural cells include craniofacial disorders as well as development of the eye and the systems it relies upon (Trainor, 2010) (Weigele & Bohnsack, 2020). 

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