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Description
Farzaneh Mohajerani1 Michael Hagan1

1, Brandeis University, Waltham, Massachusetts, United States

Bacterial Microcompartments (BMC) are roughly icosahedral shells found in bacteria that sequester enzymes involved in certain metabolic processes. Experiments suggest that some BMCs assemble by a pathway in which the enzymatic cargo first undergoes phase separation, after which the shell assembles around the dense cargo droplet. Other types of BMCs assemble in a single step, with simultaneous cargo coalescence and shell assembly. Computational studies suggest that the strength of interactions between cargo particles are a key determinant of the assembly pathway. However, the physical origins of these interactions remain unclear; in particular, whether they result from direct attractions between enzymes or are mediated by scaffolding proteins.
In this presentation we describe coarse-grained computational and theoretical modeling to study the effect of cargo interactions and cargo topology on microcompartment assembly. We present results of dynamical simulations that compare shell assembly when cargo coalescence is driven by direct cargo-cargo attractions or scaffold-mediated attractions. We find that cargo properties can dramatically influence assembly pathways. Depending on conditions, the presence of cargo may increase or decrease shell size in comparison to the intrinsic protein curvature. This result may explain recent experiments on different BMC systems in which empty BMC shells were respectively smaller or larger than full shells. In comparison to direct cargo-cargo attractions, our simulations identify a richer set of assembly behaviors for scaffold-mediated cargo attractions, and suggest that there are experimentally distinguishable differences between the two classes of systems. Understanding factors that control encapsulation of cargo by self-assembling shells is the first step for reengineering BMCs to construct drug delivery vehicles or customizable nanoreactors that encapsulate a programmable set of enzymes.

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