Cell Communication During Growth

By Sarah MooreReviewed by Sophia Coveney

Cell communication is vital to ensuring essential human functions, including growth. While scientists understand the pathways involved in growth, important questions remain regarding the nature of growth at a cellular level. Recently, scientists have explored the hypothesis that cells communicating together, in a multicellular sensing process, are able to more easily sense gradients of a growth factor, facilitating growth.

Image Credit: Billion Photos/Shutterstock.com

Cell communication in multicellular organisms

Cell communications are vital for the transmission of important biological information. Communication ensures that cells divide properly, facilitates the cohesive working of the brain together with the central nervous system, allows a vast range of neurological processes to occur such as speech, sight, comprehension, auditory processes, movement, and more. Finally, cell communication is also essential to stimulating growth, maintaining it, and stopping it when necessary.

In mammalian organisms, there are four basic categories of cellular signaling: paracrine signaling, autocrine signaling, endocrine signaling, and signaling by direct contact. Growth is directed by endocrine signaling, which involves sending hormones over long distances via the bloodstream to targeted cells and tissues to effect an action. In the case of growth, the growth hormone (GH) is sent from the pituitary gland to various cell types to induce growth. When GH reaches target cells it instructs them to divide and multiply, causing the body to grow taller and stronger.

The emerging role of cell communication in human growth

While cell communication is a key aspect of human growth, scientists are still exploring the intricacies of its nature. Recently, studies have gained evidence to show the benefits of collective cell-to-cell communication in stimulating growth.

A 2016 study showed experimentally that, while individual epithelial cells cannot sense very weak gradients of a growth factor, when acting as a cellular collective in a culture they are very reliable at producing gradient-driven and directional growth.

These findings highlight the importance of collective cell-to-cell communication and computation in growth. Out of this research, scientists have been able to validate and develop a biophysical theory of cellular communication and have identified its underlying mechanisms.

When exposed to identical cues, isogenic cells behave with a great deal of variability. Studies have shown that cells in a population will display significant variation in their gradient sensitivity and migration trajectory although they have been introduced to the same gradient of a diffusible guidance signal.

Scientists hypothesize that this variation is due to an inherent variation in cell responsiveness. Additionally, it is believed that this variation can be magnified if the extracellular signal gradients are noisy and shallow. Research has shown that sensing shallow gradients approaches the physical limits that determine if diffusive graded cues can influence cell migration.

This biased response and its uncertainty can be improved if individual cells are coupled at the time of being exposed to molecular gradients. Evidence suggests that strong cell-to-cell coupling may be effective in averaging the responses of multiple cells, and, therefore, reducing noise. Additionally, it can expand the spatial range of sensing, thus reducing sensory noise and increasing the probability of precisely detecting spatially graded inputs that are weak and noisy.

However, scientists debate whether the benefits of cell-to-cell communication in collective sensing are balanced by the fact that they themselves may be subject to noise, thus canceling out the advantage acquired from increasing the size of the sensory and response units.

With the question remaining as to whether the increased signal and accumulated communication noise limits the multicellular sensing strategy, scientists have continued to explore the nature of multicellular sensing in cell communication and growth to uncover an answer.

Scientists at Princeton University and Imperial College London recently published data in the journal PNAS (Proceedings of the National Academy of Sciences of the United States of America), revealing that mammary organoids found in collagen in humans are able to respond to shallow EGF gradients that would require collective gradient sensing and that this process is mediated via intercellular chemical coupling through gap junctions.

Interestingly, the team found that the benefit of multicellular sensing was limited and in fact lower than had been theoretically predicted by gradient sensing models due to noise not being considered. This data inspired the Princeton University/Imperial College London team to generate an accurate theory regarding the multicellular sensing process that “correctly predicts the accuracy of sensing as a function of the gradient magnitude, organoid size, and the background ligand concentration”.

The resultant theory and computational model link the reduction in sensing improvement to the noise in the information relay between cells sharing information about their local sensory measurements.

This research acts to deepen our knowledge of the role of cell communication in growth and helps to guide future research that is required to give us a full view of what this looks like at the cellular level.