  Evolution of the spatial arrangement of cells in a primary culture of cardiac
tissue derived from newborn rats was studied experimentally over extended
period. It was found that cells attract each other spontaneously to form a
clustered structure over the timescale of several days. These clusters exhibit
spontaneous rhythmic contraction and have been confirmed to consist of cardiac
muscle cells. Addition of a contraction inhibitor (2,3-butanedione-2-monoxime)
to the culture medium resulted in the inhibition of both the spontaneous
contractions exhibited by the cells as well as the formation of clusters.
Furthermore, the formation of clusters is suppressed when high concentrations
of collagen are used for coating the substratum to which the cells adhere. From
these experimental observations, it was deduced that the cells are mechanically
stressed by the tension associated with repeated contractions and that this
results in the cells becoming compact and attracting each other, finally
resulting in the formation of clusters. This process can be interpreted as
modulation of a cellular network by the activity associated with contraction,
which could be employed to control cellular networks by modifying the dynamics
associated with the contractions in cardiac tissue culture.
