As experimental physical chemists, the overall goal of our research is to understand the frequently complex structure-function relationships in biological processes and to use this information to inspire innovation for materials design. Practical goals in materials engineering include minimal cost, maximum efficiency, and optimized longevity. As our experimental and theoretical methods to study nature’s molecular-scale design principles have improved, we have begun to understand that one reason nature can be so successful is that her engineering strategy often differs from ours. Whereas humans usually design materials with a single, well-defined function, nature often acts through redundant or degenerate channels that are individually not as efficient, but collectively, and in the face of damage or wear, outperform their synthetic cousins. Obtaining clues from the biological structure-function interplay presents challenges for theory, experiment, and data analysis. When we study one molecule at a time, we eliminate ensemble averaging, thereby accessing any underlying conformational complexity. However, we must develop new methods to increase information content in the resulting low signal-to-noise single-molecule data. Thus, our research efforts have focused on three specific objectives necessary to achieve the overall goal discussed above: 1) Develop experimental data acquisition and analysis methods to optimize information retrieval in single-molecule and single-particle spectroscopies. 2) Characterize biological examples of heterogeneous structure-function relationships. 3) Identify, understand, and optimize heterogeneous structure-function relationships in synthetic systems.