Emergence of multicellular coordinated behavior by information-transfer between individual cells

A fundamental question in the study of collective behavior is how global behavior patterns emerge from individual behavior and interactions among individuals. From embryonic development, through synchronized beating of myocardiocytes to collective cell death - individual cells use basic cellular machineries to influence and respond to neighboring cells through a complex interplay of chemical and physical cues. How these heterogeneous local interactions are integrated in space and time to induce collective patterns is yet unknown.

In the first part of my talk I will briefly present one of my postdoc projects on how local mechanical fluctuations induce long-range inter-cellular communication in migrating monolayers of epithelial cells. We identified potential molecules pathways driving this mechanism and found that for effective collective migration contractility-mediating pathways must be optimally tuned to compromise between generation of motility forces and restriction of inter-cellular communication.

In the second part I will present preliminary results from my new lab at BGU on the quantification of information-transfer between individual cells in a variety of biological systems: collective cell death, mechanical interactions of cells through the extracellular matrix and collective calcium signaling. I will focus on the latter system, a monolayer of fibroblast cells that gradually synchronizes its collective calcium signal through gap junctional cell-cell communication, we discovered that cells take different roles in intercellular communication, such as leading or following cues from cells around them. By periodically applying a global external mechanical stimulus we found that individual cells maintain their roles in intercellular communication, suggesting the existence of phenotypic memory. Cells gradually learn what cells to “trust” as their leaders,potentially by integrating information along many cell-cell communication trajectories in the multicellular network. Finally, we found that the response of a cell to external cues is correlated with its susceptibility tobeing influenced by other cells, suggesting that early responder cells take the “follower” role in the multicellularnetwork.