New Model for Understanding Mechanisms of Biological Signaling: Direct Transport via Cytonemes

摘要

Biological signaling is a crucial natural process that governs the formation of all multicellular organisms. It relies on efficient and fast transfer of information between different cells and tissues. It has been presumed for a long time that these long-distance communications in most systems can take place only indirectly via the diffusion of signaling molecules, also known as morphogens, through the extracellular fluid; however, recent experiments indicate that there is also an alternative direct delivery mechanism. It utilizes dynamic tubular cellular extensions, called cytonemes, that directly connect cells, supporting the flux of morphogens to specific locations. We present a first quantitative analysis of the cytoneme-mediated mechanism of biological signaling. Dynamics of the formation of signaling molecule profiles, which are also known as morphogen gradients, is discussed. It is found that the direct-delivery mechanism is more robust with respect to fluctuations in comparison with the passive diffusion mechanism. In addition, we show that the direct transport of morphogens through cytonemes simultaneously delivers the information to all cells, which is also different from the diffusional indirect delivery; however, it requires energy dissipation and it might be less efficient at large distances due to intermolecular interactions of signaling molecules.