Cell signaling under external stimulation is a critical mechanism that governs many biological processes such as cell proliferation, cell migration, and cell apoptosis, etc. For multicellular organisms, the ability to synchronize heterogeneity individual cellular responses through intercellular communication is crucial to maintain normal functionality. However, even though the biological pathways and molecular basis of signaling and intercellular communication has been well-studied, it is still little to know about the underlying mechanisms that cells utilize to achieve highly cooperative and synchronized responses. Since molecule exchange between neighboring cells through intercellular communication will inherently be leading to the information exchange, we utilized a statistical test called granger causality test to uncover the information flow between neighboring cells communicated through gap junction. First, we applied the test on calcium signaling data from 2D neuron monolayer network being stimulated by periodic ATP stimulation. By changing the period and ATP concentration of the stimulation, we noticed that the multicellular information network constructed was dominated by the temporal signal of the stimulation, and the network evolution maintained stationary and detailed balance. The result also suggests that the multicellular network is regulated internally by intercellular communication and externally by temporal signal of the stimulation. Next, we focused on analyzing the calcium signaling caused by shear stress stimulation from human umbilical vein endothelial cells (HUVEC). Our results point out that cells can gradually adapt and learn their microenvironment which further stabilized their inner state in multicellular network architecture. This process supports the information flow from local to global scale toward synchronization. Next, we are tuning the intercellular communication by micropatterning technique that can control the shape of cell monolayer. By introducing geometrical barriers that cell cannot across, the modification of intercellular communication leading to results suggesting an interplay of intercellular communication and temporal signal in contributing to synchronization where strong intercellular communication hinders synchronization under long-period stimulation but promotes synchronization under short-period stimulation. Overall, our study provides new aspects on how external stimulation can regulate intercellular synchronization by investigating the synchronization among single-cell level signaling.