Nanoscale ligand density modulates gap junction intercellular communication of cell condensates during chondrogenesis

Abstract

Gap junction intercellular communication (GJIC) provides a continuous and efficient flow of biological information during tissue formation and is essential to sustain homeostasis and function in living organisms. Cell-matrix interactions have been widely addressed and their influence on tissue organization is recognized. However, how extracellular matrix (ECM) adhesion affects intercellular communication during tissue formation remains elusive. Here we use substrates with uneven nanopatterns of adhesive ligand arginine-glycine-aspartic acid (RGD) to control cell adhesion during mesenchymal condensation, a prevalent morphogenetic transition. We show that the establishment of GJIC is an adhesion-gated mechanism, which is dynamically regulated. Substrate effects continuously propagate into the forming tissue through actomyosin contraction, affecting both the 3D architecture and functionality of the GJIC network developing in prechondrogenic condensates.