Mechanosensing view of SARS-CoV-2 infection by a DNA nano-assembly

The mechanical force between a virus and its host cell plays a critical role in viral infection. However, characterization of the virus-cell mechanical force at the whole-virus level remains a challenge. Herein, we develop a platform in which the virus is anchored with multivalence-controlled aptamers to achieve transfer of the virus-cell mechanical force to a DNA tension gauge tether (Virus-TGT). When the TGT is ruptured, the complex of binding module-virus-cell is detached from the substrate, accompanied by decreased host cell-substrate adhesion, thus revealing the mechanical force between whole-virus and cell. Using Virus-TGT, direct evidence about the biomechanical force between SARS-CoV-2 and the host cell is obtained. The relative mechanical force gap (<10 pN) at the cellular level between the wild-type virus to cell and a variant virus to cell is measured, suggesting a possible positive correlation between virus-cell mechanical force and infectivity. Overall, this strategy provides a new perspective to probe the SARS-CoV-2 mechanical force.