Mucins have been ascribed both pro- and anti-adhesive functions. To clarify how both functions can be embodied in the same molecule we studied the interaction of human ocular mucins with mica and with mucins deposited on mica. Adhesion energy and forces of interaction were evaluated as a function of speed of approach, dwell time at maximum extension, and presence of divalent cations in the imaging buffer. Mucins were tethered to an AFM gold-coated tip. Repeated cycles of approach and retract to mica revealed a large number of adhesions in each cycle. Adhesion energy (0.2-48 aJ) and detachment forces (0.1-4 nN) increased with the addition of Ni(II) ions, and with lengthening dwell time. Speed of approach made little difference to the interactions. Most detachments occurred less than 40 nm from the surface. Inter-detachment distances reflected the major periodicities of the mica basal plane. Short distances of interaction, magnitude of detachment forces, and imaging of mucins on SAM all suggest deformable compact mucin aggregates on the AFM tip. Inter-detachment distances suggest a large degree of interpenetration between neighboring molecules. Tip-tethered mucins did not adhere to mucins deposited on mica. This phenomenon is analogous with the nonadherence of the mucin gels on lids and on cornea during blinking.