Integration of Molecular Signaling into Multiscale Modeling of Cancer - Multiscale Computer Modeling in Biomechanics and Biomedical Engineering - page 378

Fig. 1 Assume a cell's current phenotype is quiescence and the on-site nutrition is sufficient so
the cell will not die. The cell's phenotype at the next step is determined as follows. The cell will
remain quiescent if both ROC PLCc and ROC ERK remain below their corresponding thresholds
(T PLC and T ERK , respectively); the cell will proliferate (and a new cell will then occupy an
adjacent free location) if only ROC ERK exceeds T ERK ; and the cell will migrate to an adjacent
free location if ROC PLCc (regardless of ERK) exceeds T PLC
2.1.3 Molecularly Driven Cellular Phenotype Decision
PLCc is known to be involved in directional cell movement in response to EGF
[ 30 ] and is activated transiently in cancer cells, to a greater extent during migration
and more gradually in the proliferation mode [ 31 ]. Derived from this finding,
PLCc is modeled as the decision molecule for determining a cell's migratory fate
by comparing the current rate of change (ROC PLCc ) to a pre-specified threshold
T PLC . That is, if ROC PLC exceeds T PLC , the cell then has the ''potential'' to
migrate. However, a cell additionally has to meet other microenvironmental
requirements, such as sufficient local nutrient conditions and available adjacent
space, in order to process any phenotype transitions. If any of these conditions are
not met, then the cell will have to remain in its current location, waiting for the
next iteration in the simulation when conditions will be re-evaluated. Figure 1
schematically illustrates the cell phenotype decision algorithm. In addition to using
PLCc to determine the cell migration fate, ERK has been employed in making cell
proliferation decision, also based on experimental evidence [ 32 ].