Life as we know it could scarcely exist in the absence of specific interact
ions between its molecular and supramolecular components. At every stage in
the existence of a living organism, specificity intervenes to ensure that
chance encounters are selectively guided towards further interaction. This
applies to the reactions directing the development of a complex multicellul
ar organism, enzyme catalysis, the immune response, etc. The efficiency of
searching for specific interaction partners can be greatly increased by red
ucing the dimensionality of the search space. Selectivity is enhanced by im
posing a requirement for multiple binding events, within constraints of eit
her time or space, in order to actuate a response. Most biological macromol
ecules can exist in several stable conformational states, and switching bet
ween them (conformational change) following the initial encounter between t
wo biomolecules enables specificity to be further enhanced. The experimenta
l determination of the parameters governing biomolecular interactions needs
high resolution binding assays carried out under well defined hydrodynamic
conditions. Optical waveguide lightmode spectrometry (OWLS) is well able t
o fulfil these requirements. Illustrative examples using this technique are
presented, demonstrating the enzymatic decomposition of polylysine, the li
pid head group selectivity of actin filament polymerization and the influen
ce of both head group and internal bilayer membrane structure on perforin b
inding. (C) 2000 Elsevier Science B.V. All rights reserved.