Oster, L. F. | Search bioRxiv

bioRxiv2026

Environment-driven active transport of influenza A virus

Biological media such as airway mucus and extracellular matrix are usually viewed as transport barriers that particles cross by passive diffusion or with internal engines. We show instead that a particle can move actively by modifying the landscape it traverses, creating environmental memory and directional cues in two and three dimensions. Influenza A virus (IAV) realizes this principle through its envelope proteins hemagglutinin (HA) and neuraminidase (NA), which bind and cleave sialylated glycan receptors, respectively. Combining theory, simulations and single-virus tracking, we connect bind--cleave kinetics and HA--NA organization to macroscopic transport. Cleavage dissipates chemical free energy, biases rebinding to the edited landscape and leaves a trail that shapes future encounters. In heterogeneous receptor landscapes, multivalent binding biases motion toward higher receptor density, while receptor destruction by NA can amplify this bias by sharpening the contrast sampled by HA. Experiments on reconstituted glycan membranes show that IAV steps are biased up local receptor gradients, as predicted. The theory suggests that virion-to-virion variability can distribute transport functions across a population, providing a physical hedge against complex receptor environments. Together, these results establish environment-driven active matter as a mechanism for motorless transport powered and guided by chemical modification of the environment.

biophysics↗

bioRxiv2024

Cell surface crowding is a tunable biophysical barrier to cell-cell fusion

Cell-cell fusion is fundamental to developmental processes such as muscle formation, as well as to viral infections that cause pathological syncytia. An essential step in fusion is close membrane apposition, but cell membranes are crowded with proteins, glycoproteins, and glycolipids, all of which must be cleared before a fusion pore can be nucleated. Here, we find that cell surface crowding drastically reduces fusogenicity in multiple systems, independent of the method for driving fusion. We estimate that cell surface crowding presents an energetic barrier to membrane apposition on the scale of [~]100kBT, greater than that of bare membrane fusion. We show that increasing cell surface crowding reduces fusion efficiency of PEG-mediated and fusogen-mediated cell-cell fusion, as well as synthetic membranes under force. Interestingly, we find that differentiating myoblasts naturally decrease cell surface crowding prior to fusion. Cell surface crowding presents an underappreciated biophysical barrier that may be tuned developmentally and could be targeted externally to control tissue-specific cell-cell fusion.

biophysics↗