Mind the gap: A mechanobiological hypothesis for the role of gap junctions in the mechanical properties of injured brain tissue

Abstract Despite more than half a century of work on the brain biomechanics, there are still significant unknowns about this tissue. Since the brain is highly susceptible to injury, damage biomechanics has been one of the main areas of interest to the researchers in the field of brain biomechanics. In many previous studies, mechanical properties of brain tissue under sub-injury and injury level loading conditions have been addressed; however, to the best of our knowledge, the role of cell-cell interactions in the mechanical behavior of brain tissue has not been well examined yet. This note introduces the hypothesis that gap junctions as the major type of cell-cell junctions in the brain tissue play a pivotal role in the mechanical properties of the tissue and their failure during injury leads to changes in brain's material properties. According to this hypothesis, during an injury, the gap junctions are damaged, leading to a decrease in tissue stiffness, whereas following the injury, new junction proteins are expressed, leading to an increase in tissue stiffness. We suggest that considering the mechanobiological effect of gap junctions in the material properties of brain tissue may help better understand the brain injury mechanism.