A Materials Genome Approach to Understanding Biofilm Mechanics

A Materials Genome Approach to Understanding Biofilm Mechanics Biofilms are highly evolved, efficient bacterial colonies that exhibit outstanding adhesive strength once formed on surfaces. The tenacity of biofilms to bind indifferently to substrates is attributed to the extracellular matrix proteins called functional amyloids, most notably, the curli nanofibers found in E. coli biofilms. Curli nanofibers regulate matrix elasticity, intercellular cohesion within the biofilm, and most remarkably, nonspecific adhesion to surfaces. With recent breakthroughs in genetic engineering of E. coli, it is possible to synthesize biofilms with diverse functions that are attained by conjugating small peptides onto curli nanofibers. Both natural and genetically modified curli nanofibers achieve outstanding adhesive and cohesive strength, but the fundamental mechanism governing this phenomenon is still unknown. Biofilms are an exciting new frontier in synthetic biology because control of the curli nanofiber features through genetic engineering serves as an enabling tool to synthesize a new class of self-assembling protein materials. The bacterial genome is well-characterized and can now be manipulated to achieve unprecedented adhesive and cohesive properties through rational design of the extracellular protein networks. However, a number of obstacles exist that hinder our capability to predict biofilm mechanics in relation to their genetics. First, the molecular mechanisms through which curli nanofibers achieve outstanding intercellular and interfacial adhesion are still not well understood. Second, the role of different constituents on the structural and mechanical properties of biofilms has yet to be determined through a holistic multi-scale viewpoint. Third, a predictive modeling approach to linking the cellular genome (genetic makeup), mechanome (mechanics of curli nanofibers) and biofilm materiome (material performance) remains elusive. A closed loop linking the bacterial genome to the mechanome of the cells, and ultimately the materiome of biofilms will allow us to understand and improve upon biological design principles. To address this issue, the objective of the proposed research is to establish a materials genome approach to understanding the mechanics of biofilms. The two aims that will be pursued in light of this overarching objective are: • Aim 1 - Elucidate the adhesive and cohesive properties of curli nanofibers • Aim 2 - Establish a mesoscopic model for biofilm adhesion and detachment Through computational approaches validated by experimental characterizations, we will be able to predict biofilm adhesion and cohesion characteristics from the shape, size, architecture and surface chemistry of curli nanofibers. In the spirit of a materials genome approach, a database for adhesive functional amyloids will be built to tailor biofilm performance through theory-driven approaches. The proposed work is central to the long-term career objective of the PI, which is to enable progress towards rapid discovery and design of bioinspired materials by establishing a knowledge base of their physical behavior relevant to applications beyond the biological milieu. This is a first effort at building a materials genome capability for natural and engineered biofilms, and the niche expertise of the PI addresses the critical need to understand nano and meso-scale mechanisms in these biosystems. The proposed research will reveal new strategies for making — and also eradicating — biofilms by deciphering the inner working m