Biofilms are implicated in serious infectious diseases and have emerged as a target for anti-infectives. Our research program is inspired by the challenge and importance of elucidating chemical structure and function in complex biological systems and we strive to transform our discoveries into new therapeutic strategies. We have introduced new approaches integrating solid-state NMR with microscopy and biochemical and biophysical tools to reveal how amyloid-associated biofilm assembly and architecture in E. coli is influenced by chemical and molecular composition. Solid-state NMR is serving as a powerful discovery tool in these efforts and we recently reported the unprecedented discovery of a naturally produced chemically modified cellulose produced by E. coli and Salmonella strains. Solid-state NMR of the intact cellulosic material enabled the elucidation of the zwitterionic phosphoethanolamine modification and we identified the genetic and molecular basis for its assembly. I will report on our efforts to understand and describe the macromolecular assembly of the amyloid-polysaccharide composites in E. coli and their relation to biofilm function.