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Figure 5.5 Attaching sheets at the tips of pipettes using matrix solutions, and then
removing the matrix, permits some basic manipulations of cell sheets. Here, the cell
sheet in (i) is pulled to 80% strain in (ii), showing that cell-cell adhesion is capable of
sustaining high deformation (
Harris et al., 2012
).
6. FUTURE RESEARCH DIRECTIONS
To fully characterize cell-cell interactions, further research is imper-
ative. The current understanding of junctional roles is still quite limited and
offers little predictive power. For example, which protein domains are major
players in cell-cell adhesion is not something that is currently known.
Indeed, quantitative measurement of cell-cell adhesion strength, at the
cell-pair level, under normal plating conditions, would be a significant
accomplishment. Note that it is insufficient to simply measure traction forces
across cell junctions, as has been done. Adhesion strength may be far larger
than exerted contraction forces.
Determination of the amount of junctional proteins within the cell, at
junctions and in other places, as well as the trafficking of such proteins, is
also of considerable interest. While junctional proteins apparently have non-
junctional roles (e.g.,
b
-catenin signaling and the canonical Wnt pathway),
much work remains to be done in mapping the various pathways and inter-
actions. Similarly, the role of junctional proteins in signaling, especially
mechanotransductive signaling, remains a rich field of exploration.
Determining the balance between cell-cell and cell-substrate interac-
tions is likely to be fruitful. The hypothesis that a cell distributes forces
between substrates and adjacent cells is gaining support via experimentation,
yet the hypothesis is not quite mature enough to provide broad predictive
power. For example, it is unknown whether all cells achieve the same force
distribution, whether all cells exhibit the same ability to shift between
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