Flow‐induced shear stresses increase the number of cell–cell contacts within extracellular matrix

Abstract

The formation of cell-cell contacts within extracellular matrix (ECM) is essential to maintain tissue homeostasis and metabolism, as well as critical toward the cell-ECM mechanotransduction that can affect intracellular organization and intercellular communication to enable cell response to external stimuli. This work illustrates the effects of shear stresses on cell-cell contacts within pre-stressed collagen ECM that were loaded in two separate conditions of constant flow (CF) and constant elution time (CET). The numbers of cell-cell contacts and cytoplasmic processes in both media and 3D ECM gels were analyzed in order to examine the shear effects of different magnitudes and time periods on 3D cell-ECM formation. The sheared collagen ECM microstructures were imaged and studied via scanning electron microscopy (SEM) to illustrate greater distances between constituent cells when larger shear stresses were applied. And the gap junction Connexin 43 expressed between networked cells that were sheared in short time period using CF loading exhibited more than those using CET loading. Notably, the number of cell-cell contacts increased when larger shear stresses were applied, suggesting these stresses may be used to increase intercellular communication within 3D matrixes.