Endothelial cells (ECs) play a crucial role in the development and propagation of the severe COVID-19 stage as well as multiorgan dysfunction. It remains, however, controversial whether COVID-19-induced endothelial injury is caused directly by the infection of ECs with SARS-CoV-2 or via indirect mechanisms. One of the major concerns is raised by the contradictory data supporting or denying the presence of ACE2, the SARS-CoV-2 binding receptor, on the EC surface. Here, we show that primary human pulmonary artery ECs possess ACE2 capable of interaction with the viral Spike protein (S-protein) and demonstrate the crucial role of the endothelial glycocalyx in the regulation of the S-protein binding to ACE2 on ECs. Using force spectroscopy method, we directly measured ACE2- and glycocalyx-dependent adhesive forces between S-protein and ECs and characterized the nanomechanical parameters of the cells exposed to S-protein. We revealed that the intact glycocalyx strongly binds S-protein but screens its interaction with ACE2. Reduction of glycocalyx layer exposes ACE2 receptors and promotes their interaction with S-protein. These results indicate that the susceptibility of ECs to COVID-19 infection may depend on the glycocalyx condition.
【저자키워드】 Biophysics, glycobiology, Atomic force microscopy, Nanoscale biophysics, Mechanisms of disease, Single-molecule biophysics, 【초록키워드】 SARS-CoV-2, ACE2, severe COVID-19, spike, susceptibility, Infection, ACE2 receptor, Protein, COVID-19 infection, mechanisms, endothelial injury, receptor, binding, Interaction, S-protein, Multiorgan dysfunction, endothelial, Regulation, parameter, Cell, bind, caused, raised, characterized, promote, the SARS-CoV-2, 【제목키워드】 ACE2 receptor, SARS-CoV-2 spike protein, Interaction,