Search for: All records

Bacterial cells can self-organize into structured communities at fluid-fluid interfaces. These soft, living materials composed of cells and extracellular matrix are called pellicles. Cells residing in pellicles garner group-level survival advantages such as increased antibiotic resistance. The dynamics of pellicle formation and, more generally, how complex morphologies arise from active biomaterials confined at interfaces are not well understood. Here, using Vibrio cholerae as our model organism, a custom-built adaptive stereo microscope, fluorescence imaging, mechanical theory, and simulations, we report a fractal wrinkling morphogenesis program that differs radically from the well-known coalescence of wrinkles into folds that occurs in passive thin films at fluid-fluid interfaces. Four stages occur: growth of founding colonies, onset of primary wrinkles, development of secondary curved ridge instabilities, and finally the emergence of a cascade of finer structures with fractal-like scaling in wavelength. The time evolution of pellicle formation depends on the initial heterogeneity of the film microstructure. Changing the starting bacterial seeding density produces three variations in the sequence of morphogenic stages, which we term the bypass, crystalline, and incomplete modes. Despite these global architectural transitions, individual microcolonies remain spatially segregated, and thus the community maintains spatial and genetic heterogeneity. Our results suggest that the memory of the original microstructure is critical in setting the morphogenic dynamics of a pellicle as an active biomaterial. 

"Seasonal influenza A viruses of humans evolve rapidly due to strong selection pressures from host immune responses, principally on the hemagglutinin (HA) viral surface protein. Based on mouse transmission experiments, a proposed mechanism for immune evasion consists of increased avidity to host cellular receptors, mediated by electrostatic charge interactions with negatively charged cell surfaces. In support of this, the HA charge of the globally circulating H3N2 has increased over time since its pandemic. However, the same trend was not seen in H1N1 HA sequences. This is counter-intuitive, since immune escape due to increased avidity (due itself to an increase in charge) was determined experimentally. Here, we explore whether patterns of local charge of H1N1 HA can explain this discrepancy and thus further associate electrostatic charge with immune escape and viral evolutionary dynamics. Measures of site-wise functional selection and expected charge computed from deep mutational scan data on an early H1N1 HA yield a striking division of residues into three groups, separated by charge. We then explored evolutionary dynamics of these groups from 1918 to 2008. In particular, one group increases in net charge over time and consists of sites that are evolving the fastest, that are closest to the receptor binding site (RBS), and that are exposed to solvent (i.e., on the surface). By contrast, another group decreases in net charge and consists of sites that are further away from the RBS and evolv- ing slower, but also exposed to solvent. The last group consists of those sites in the HA core, with no change in net charge and that evolve very slowly. Thus, there is a group of residues that follows the same trend as seen for the entire H3N2 HA. It is possible that the H1N1 HA is under other biophysical constraints that result in compensatory decreases in charge else- where on the protein. Our results implicate localized charge in HA interactions with host cells, and highlight how deep mutational scan data can inform evolutionary hypotheses."