Abstract: Synthetic cell-cell adhesins and 4-bit logic for programming multicellular interface patterns

Abstract: Synthetic cell-cell adhesins and 4-bit logic for programming multicellular interface patterns

Multicellular systems, from bacterial biofilms to human organs, form spatial patterns and interfaces
to achieve complex functionality, promising applications like programmable biomaterials, artificial
tissues, and metabolic consortia [1]. Our ability to rationally engineer such active matter is still limited. My lab recently developed the first synthetic and optogenetic approaches to control cell-cell and cellsurface adhesion for bacterial self-assembly [2] and patterning (‘Biofilm Lithography’) [3].
I will discuss the biophysical characterization of these tools and their applications to investigate
cooperative antibiotic responses in biofilms. I will then demonstrate a synthetic 4-bit cell-cell adhesin
logic to experimentally program and mathematically model universal two-dimensional interface patterns [4]. These interfaces are generated through a swarming adhesion mechanism that enables precise control over interface geometry as well as adhesion-mediated analogs of developmental organizers and morphogen fields. Utilizing tiling and four-color mapping concepts, I present algorithms for creating versatile target patterns. Remarkably, a minimal set of four adhesins suffices to program arbitrary tessellation patterns, implying a low critical threshold for the engineering and evolution of complex multicellular systems.
Finally, I will discuss ongoing and future project opportunities in my lab – particularly for modeling
genetic networks, biofilms, and bioreactors with applications for chemical synthesis, green-house gas
reduction (methane), and bioremediation.

References
[1] Kim H, Jin X, Glass DS, Riedel-Kruse IH#
Engineering and modeling of spatio-temporal patterns and morphologies in multicellular systems
Current Opinion in Genetics & Development; 2020, 63, 95.
[2] Glass D, Riedel-Kruse IH. #
A genetically encoded adhesin toolbox for programming multicellular morphologies and patterns.
Cell; 2018. 174 (3) 649–658.
[3] Jin X, Riedel-Kruse IH. #
Biofilm Lithography: High-resolution cell patterning via optogenetic adhesin expression.
PNAS; 2018. 115 (14) 3698-3703.
[4] Kim H, Skinner DJ, Glass DS, Hamby AE, Stuart BAR, Dunkel J, Riedel-Kruse IH*
4-bit adhesion logic enables universal multicellular interface patterning
Nature; 2022 608, 324–329.