Coupled left-shift of Nav channels: modeling the Na⁺-loading and dysfunctional excitability of damaged axons.

Injury to neural tissue renders voltage-gated Na⁺ (Nav) channels leaky. Even mild axonal trauma initiates Na⁺-loading, leading to secondary Ca²⁺-loading and white matter degeneration. The nodal isoform is Nav1.

Left-shifted nav channels in injured bilayer: primary targets for neuroprotective nav antagonists?

Mechanical, ischemic, and inflammatory injuries to voltage-gated sodium channel (Nav)-rich membranes of axon initial segments and nodes of Ranvier render Nav channels dangerously leaky. By what means? The behavior of recombinant Nav1.6 (Wang et al.

Mechanosensitive closed-closed transitions in large membrane proteins: osmoprotection and tension damping.

Multiconformation membrane proteins are mechanosensitive (MS) if their conformations displace different bilayer areas. Might MS closed-closed transitions serve as tension buffers, that is, as membrane "spandex"? While bilayer expansion is effectively instantaneous, transitions of bilayer-embedded MS proteins are stochastic (thermally activated) so spandex kinetics would be critical. Here we model generic two-state (contracted/expanded) stochastic spandexes inspired by known bacterial osmovalves (MscL, MscS) then suggest experimental approaches to test for spandex-like behaviors in these proteins.

Pore formation in a lipid bilayer under a tension ramp: modeling the distribution of rupture tensions.

The rupture of fluid membrane vesicles with a steady ramp of micropipette suction has been shown to produce a distribution of breakage tensions, with a mean that rises rapidly with tension rate. Starting from a lattice model that incorporates the essential features of the lipid bilayers held together with hydrophobic forces, and developing it to handle varying tension rates, we reproduce the main features of the experimental results. In essence, we show that the rupture kinetics are driven by the nucleation and growth of pores, with two limiting kinetics-growth-limited and nucleation-limited.