The force measurements show that, in the 6-and 7-repeat versions of DC-SIGNR, stable tetramers form a rigid neck region that projects the CRDs away from the membrane, ensuring strong, multivalent adhesion to the target membrane. These variants have comparable adhesion energies and solution binding affinities. However, disruption of the tetramer in the 5-repeat variant both produces a more flexible/compressible molecule and substantially reduces the adhesion. Further, loss of neck repeats in this variant reduces the extension of the CRDs from the membrane surface-a feature that could reduce access to pathogens.