Protein corona can significantly alter the interfacial physico-chemical characteristics and hydrodynamics of microentities in crowded bio-fluids. However, how this soft boundary affects the confined motion and intersurface interaction remains unknown. In this study, we used total internal reflection microscopy to directly measure the mechanical coupling underlying the confinement. By tuning ionic strength, pH, and surface chemistry, we observed that the confined motion transitioned from Fickian diffusion to a sublinear behavior, where the displacements normal to the wall consistently exhibit a non-Gaussian distribution. This abnormal phenomenon, especially for stuck particles, results in a mechanical-reversal asymmetry, as evidenced by the intersurface potential energy profiles. The multiscale-dependent mechanism for soft boundaries under deformation can be correlated with the hydration layer and inherent Hookean elasticity of protein corona. These observations hold across a wide variety of near-wall confinement spanning from superhydrophilic to hydrophobic substrates, and further to bio-interfaces.
