The assembly of integral membrane protein complexes is frequently supported by transmembrane domain (TMD) interactions. Here, we present the BLaTM assay that measures homotypic as well as heterotypic TMD-TMD interactions in a bacterial membrane. The system is based on complementation of β-lactamase fragments genetically fused to interacting TMDs, which confers ampicillin resistance to expressing cells. We validated BLaTM by showing that the assay faithfully reports known sequence-specific interactions of both types. In a practical application, we used BLaTM to screen a focussed combinatorial library for heterotypic interactions driven by electrostatic forces. The results reveal novel patterns of ionizable amino acids within the isolated TMD pairs. Those patterns indicate that formation of heterotypic TMD pairs is most efficiently supported by closely spaced ionizable residues of opposite charge. In addition, TMD heteromerization can apparently be driven by hydrogen bonding between basic or between acidic residues.

In diabetes, hyperamylinemia contributes to cardiac dysfunction. The interplay between hIAPP, blood glucose and other plasma components is, however, not understood. We show that glucose and LDL interact with hIAPP, resulting in β-sheet rich oligomers with increased β-cell toxicity and hemolytic activity, providing mechanistic insights for a direct link between diabetes and cardiovascular diseases.

Deformation and dynamic flow behaviour of nucleated duck erythrocytes were compared to those of nonnucleated human cells during steady flow (at wall shear stresses up to 3 N.m-2) through glass capillaries (diameter between 5 micrometer and 12 micrometer). While the deformation process of both cell species is qualitatively similar, significant quantitative differences demonstrate a lower deformability of the nucleated erythrocytes. In comparison to human cells, the avian red cells exhibit significantly lower stability of orientation during capillary flow. Viscometric measurements show that, in contrast to human red cell suspensions, the relative viscosity of nucleated cell suspensions does not decrease with increasing suspending medium viscosity. The results indicate that the hydrodynamic disturbance caused by avian erythrocytes in the flow of the suspending fluid is more pronounced than that of the mammalian cells. This is due to their lower ability to adapt to local shear forces.