Events & Seminars > Event Details


3:00 pm
Room 304, Chemistry Building

Cargo encapsulation by self-assembling icosahedral containers


Professor Mike Hagan
Brandeis University

Hosted by: Professor Kateri DuBay

The self-assembly of a protein shell around a cargo is a common mechanism of encapsulation in biology, and is inspiring development of drug delivery vehicles that form by self-assembly. However, the physics underlying such multicomponent assembly processes is incompletely understood. In this talk I will describe how minimal computational models can elucidate two biological examples in which icosahedral protein shells assemble around cargos. In each case we find that the material properties of the cargo play a key role in directing its encapsulation.

The first example concerns viruses with single-stranded RNA (ssRNA) genomes. For many ssRNA viruses, formation of an infectious virus requires the spontaneous assembly of an icosahedral protein shell (called a capsid) around the genome. I will describe simulations that investigate how this co-assembly process depends on the physical properties of RNA: its length, electrostatic charge, and 3D structure. When applied to specific virus capsids, the calculated optimal RNA lengths closely correspond to the natural viral genome lengths. This suggests that evolution of viral RNA is driven not only by the fitness of the proteins that it encodes for, but also by how its material properties favor encapsulation. We then show that assembly can proceed through two qualitatively different classes of pathways, which can be tuned by solution conditions or changing the capsid protein properties.

The second example concerns carboxysomes, which are large, roughly icosahedral protein shells that facilitate carbon fixation in cyanobacteria. Carboxysomes assemble around a cargo which is topologically different from ssRNA, a noncovalently linked, amorphous complex of the enzyme RuBisCO. Motivated by this problem, we study assembly of icosahedral shells around a fluid cargo. We find different assembly pathways and different critical control parameters as compared to assembly around RNA, and that the predominant assembly pathway depends strongly on the cargo fluidity. We discuss relationships between simulated assembly pathways and recent experiments observing assembly of individual carboxysomes in bacteria.


Michael Hagan is Associate Professor of Physics and of Quantitative Biology at Brandeis. He received a BSE and PhD in Chemical Engineering respectively from the University of Connecticut and University of California at Berkeley. Michael’s lab uses computational modeling and theory to understand the physical principles that control assembly and dynamical organization in biological, biomimetic, and other soft condensed matter systems. Because assembling structures can be orders of magnitude larger than the individual components that comprise them, the lab develops and apply computational and theoretical methods that bridge disparate length and time scales. Applications include understanding the assembly of viral capsids and other large protein complexes, discovering the mechanisms by which proteins interconvert between different conformations, and understanding emergent behaviors in active matter systems (materials whose constituent elements consume energy to generate motion, such as the internal components of a cell).