Collaborative Research: Mechanics and Morphogenesis in Biofilms: A Model System of Adaptive Growth

About This Grant

Growth is a quintessential feature of all living systems; understanding the mechanics of growth is crucial in a wide range of ecological, industrial, and medical settings. However, while there is an increasing appreciation for the significant role of mechanics in defining the growth and form of biological materials, the field has yet to provide a basic understanding of key mechano-morphogenesis processes and their sensitivity to various environmental factors, such as geometrical constraints and nutrient availability. To address this question, this collaborative project takes advantage of a highly tunable biological system that is capable of macroscale growth - bacterial biofilms. Confocal imaging and analysis of the growth process will enable detailed observation of various growth phenomena at both single-cell and continuum levels and can measure the influence of environmental factors. The parallel theoretical effort will stem from the derivation of theoretical models that integrate only the essential ingredients by which the biological system evolves to provide an open-ended strategy to explore and expose rules and unexpected phenomena in morphogenesis. The research is likely to have direct implications for our understanding of the development and resilience of bacterial biofilms. The overarching goal of this collaborative research is two-fold: 1) to deepen the understanding of the development of biofilms in constrained environments; 2) to leverage the growth of highly tunable biofilm systems as a generic scheme for biological growth. The approach focuses on the development of theoretical models that are complex enough to contain the essential coupled mechanisms involved in growth and morphogenesis but are simple enough to explain the basic phenomena that may emerge and can serve as tools to expose additional unexpected phenomena. The first two objectives of this work study the separate roles of nutrient transport and mechanical stress using specially designed experimental setups that isolate the specific phenomena of interest in the embedded biofilm system. The third objective further iterates between the theory and the experiments to capture the coupling between the different mechanisms and to explore ranges of response that are beyond reach of the experimental system. The models developed and the conclusions from the observations of the bacterial biofilms system confined in hydrogels, in this work, can be applied to other cellular collectives or biological entities growing under mechanical constraints. These insights can thus lead to several biomedical applications, and opens new directions for studies on embedded biofilms, such as their antibiotic resistance. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.