The development of materials that undergo shape changes occupies a central theme in materials science and has proven important in several applications. Several classes of hydrogels, which are cross-linked water-soluble polymers, can change their properties (such as, volume, cross-link density) in response to temperature, pH value, or ionic strength. [1][2][3][4][5] These dynamic hydrogels can also be modified with biochemical moieties to give materials that change their properties in response to proteins and ligands. [3,6] For example, hydrogels that undergo volume changes because of antigen-antibody [2] and lectin-carbohydrate [7,8] interactions have been used as biosensors. The underlying principle of operation of dynamic hydrogel materials relates to a change in their physical or chemical cross-linking density in response to environmental cues. An unexplored alternative to these approaches relies on the use of a natural protein that undergoes a conformational change as a mechanism to alter the characteristics of a material. The functional importance of protein motions in biological systems, together with the wide range of protein motions that can be harnessed, offers a flexible approach to the preparation of dynamic materials. We describe herein an example of a protein-based dynamic material, the functional nature of which is derived from the conformational properties of the protein calmodulin (CaM). Calmodulin is a 16.5-kDa protein with two distinct conformational states (Figure 1). [9][10][11][12][13] In the presence of calcium ions, CaM has an extended, dumbbell-shaped conformation (herein termed "extended CaM"). [14] This calciumbound CaM undergoes a transition from an extended dumbbell to a collapsed conformation (herein termed "collapsed CaM") [15] upon the binding of ligands, which include certain antipsychotic drugs (such as, trifluoperazine (TFP)), [10,13,16] peptides, [9] and a variety of proteins [12] . Recently, Daunert and co-workers described a class of hydrogels that incorporate CaM and a small-molecule ligand as pendant moieties within the network. [17] The binding of the CaM units and ligands resulted in an increased cross-linking density and a decreased swelling of the network. This approach is analogous to the development of dynamic hydrogels based on antigen-antibody [2] and lectin-carbohydrate [7,8] interactions, but differs