Deep mutational scanning reveals EGFR mutations conferring resistance to the 4th-generation EGFR tyrosine kinase inhibitor BLU-945.

Fourth-generation EGFR tyrosine kinase are in development to overcome common resistance mutations. We performed deep mutational scanning (DMS) of the EGFR kinase domain in the context of L858R by introducing a saturation library of ~17,000 variants into Ba/F3 cells. DMS library-expressing cells were exposed to osimertinib or BLU-945 to identify escape mutations.

Competing instabilities reveal how to rationally design and control active crosslinked gels.

How active stresses generated by molecular motors set the large-scale mechanics of the cell cytoskeleton remains poorly understood. Here, we combine experiments and theory to demonstrate how the emergent properties of a biomimetic active crosslinked gel depend on the properties of its microscopic constituents. We show that an extensile nematic elastomer exhibits two distinct activity-driven instabilities, spontaneously bending in-plane or buckling out-of-plane depending on its composition.

Microcompartment assembly around multicomponent fluid cargoes.

This article describes dynamical simulations of the assembly of an icosahedral protein shell around a bicomponent fluid cargo. Our simulations are motivated by bacterial microcompartments, which are protein shells found in bacteria that assemble around a complex of enzymes and other components involved in certain metabolic processes. The simulations demonstrate that the relative interaction strengths among the different cargo species play a key role in determining the amount of each species that is encapsulated, their spatial organization, and the nature of the shell assembly pathways.