The ability to measure kT- and nanometer-scale potentials of mean force between proteins provides a fundamental basis to understand many problems in biology and medicine. Yet, the current state-of-the-art in measuring protein interactions is generally limited to mechano-chemical measurements of binding pair off-rates or spectroscopic interrogation of ensemble dissociation constants. In this talk, we describe the use of freely diffusing colloids as probes of thermally accessible, equilibrium interactions between cadherin fragments (cell-cell adhesion protein superfamily) covalently attached and oriented on lipid bilayers supported on colloid and wall surfaces. In particular, two separate methods involving diffusing colloidal probes are employed to measure the Ca²⁺ dependence of homophilic cadherin interactions. In the first method, video microscopy is used to measure particle pair distribution functions from which particle pair potentials are obtained via inverse Monte Carlo analyses. In the second method, integrated evanescent wave scattering and video microscopy are used to simultaneously measure single and ensemble particle-wall interactions to yield both equilibrium potentials and association dynamics. All measurements are performed in physiological ionic strength buffers with varying [Ca²⁺] to obtain information on short-range, protein-protein potentials. The use of different particles sizes and supported lipid bilayers is exploited in this work to provide flexible control over protein surface density, lateral mobility, and number of parallel association events. Ongoing work is extending these approaches to sensitively interrogate heterophilic cadherin interactions using homophilic interactions from the present work as a baseline.