A method for crosslinking one or more molecules comprises crosslinking the one or more molecules with a photactivatable crosslinker by one-photon or multi-photon excitation, wherein the crosslinker comprises at least two photoactive groups linked by a bridging moiety, and further wherein the point volume of the activation has at least one dimension of less than about 1 micron. The method is of particular utility for water-soluble molecules, particularly biologically active water-soluble molecules.