Nonuniform growth and surface friction determine bacterial biofilm morphology on soft substrates. Author Chenyi Fei, Sheng Mao, Jing Yan, Ricard Alert, Howard Stone, Bonnie Bassler, Ned Wingreen, Andrej Košmrlj Publication Year 2020 Type Journal Article Abstract During development, organisms acquire three-dimensional (3D) shapes with important physiological consequences. While basic mechanisms underlying morphogenesis are known in eukaryotes, it is often difficult to manipulate them in vivo. To circumvent this issue, here we present a study of developing biofilms grown on agar substrates in which the spatiotemporal morphological patterns were altered by varying the agar concentration. Expanding biofilms are initially flat but later undergo a mechanical instability and become wrinkled. To gain mechanistic insights into this dynamic pattern-formation process, we developed a model that considers diffusion of nutrients and their uptake by bacteria, bacterial growth/biofilm matrix production, mechanical deformation of both the biofilm and the substrate, and the friction between them. Our model shows quantitative agreement with experimental measurements of biofilm expansion dynamics, and it accurately predicts two distinct spatiotemporal patterns observed in the experiments-the wrinkles initially appear either in the peripheral region and propagate inward (soft substrate/low friction) or in the central region and propagate outward (stiff substrate/high friction). Our results, which establish that nonuniform growth and friction are fundamental determinants of stress anisotropy and hence biofilm morphology, are broadly applicable to bacterial biofilms with similar morphologies and also provide insight into how other bacterial biofilms form distinct wrinkle patterns. We discuss the implications of forming undulated biofilm morphologies, which may enhance the availability of nutrients and signaling molecules and serve as a "bet hedging" strategy. Keywords Biofilms, Biomechanical Phenomena, Vibrio cholerae, Stress, Mechanical, Surface Properties, Anisotropy, Agar, Friction Journal Proc Natl Acad Sci U S A Volume 117 Issue 14 Pages 7622-7632 Date Published 2020 Apr 07 ISSN Number 1091-6490 DOI 10.1073/pnas.1919607117 Alternate Journal Proc Natl Acad Sci U S A PMCID PMC7148565 PMID 32193350 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML