The what, when, where, and why of wrinkly morphology in biofilms

Wrinkling is a striking emergent behavior that occurs in microbial biofilms across many species. The phenomenon originates from an intricate interplay between environmental factors, cell-to-cell phenotypic heterogeneity, and mechanical forces, thus requiring insights from multiple disciplines, from biology through chemistry to physics, to be fully understood. We critically review current knowledge about wrinkle formation in biofilms, starting with an analysis of the shared and distinct features that characterize this morphology across different species and the potential evolutionary advantages associated with it. Leveraging the vast literature on Bacillus subtilis, we then focus on its biofilms to discuss in detail the molecular mechanisms and regulation of wrinkle formation, along with the environmental factors that impact this phenotype. We follow by summarizing the insights gained from theoretical and modeling work on the mechanical origin of wrinkle formation, and the related experimental studies that have attempted to measure the material properties of different biofilms. We conclude with a synthesis of the many physical, chemical, and biological factors at play and a discussion of the remaining open questions around complex architectures in biofilms.