Mobility Measurements Probe Conformational Changes in Membrane Proteins due to Tension

The function of membrane-embedded proteins such as ion channels depends crucially on their conformation. We demonstrate how conformational changes in asymmetric membrane proteins may be inferred from measurements of their diffusion. Such proteins cause local deformations in the membrane, which induce an extra hydrodynamic drag on the protein. Using membrane tension to control the magnitude of the deformations and hence the drag, measurements of diffusivity can be used to infer--- via an elastic model of the protein--- how conformation is changed by tension. Motivated by recent experimental results [Quemeneur et al., Proc. Natl. Acad. Sci. USA, 111 5083 (2014)] we focus on KvAP, a voltage-gated potassium channel. The conformation of KvAP is found to change considerably due to tension, with its `walls', where the protein meets the membrane, undergoing significant angular strains. The torsional stiffness is determined to be 26.8 kT at room temperature. This has implications for both the structure and function of such proteins in the environment of a tension-bearing membrane.Comment: Manuscript: 4 pages, 4 figures. Supplementary Material: 8 pages, 1 figur

Composition variation and underdamped mechanics near membrane proteins and coats

We study the effect of membrane proteins on the shape, composition and thermodynamic stability of the surrounding membrane. When the coupling between membrane composition and curvature is strong enough the nearby composition and shape both undergo a transition from over-damped to under-damped spatial variation, well before the membrane becomes unstable in the bulk. This transition is associated with a change in the sign of the thermodynamic energy and hence has the unusual features that it can favour the early stages of coat assembly necessary for vesiculation (budding), while suppressing the activity of mechanosensitive membrane channels and transporters. Our results also suggest an approach to obtain physical parameters that are otherwise difficult to measure

Density regulation in strictly metric-free swarms

There is now experimental evidence that nearest-neighbour interactions in flocks of birds are metric free, i.e. they have no characteristic interaction length scale. However, models that involve interactions between neighbours that are assigned topologically are naturally invariant under spatial expansion, supporting a continuous reduction in density towards zero, unless additional cohesive interactions are introduced or the density is artificially controlled, e.g. via a finite system size. We propose a solution that involves a metric-free motional bias on those individuals that are topologically identified to be on an edge of the swarm. This model has only two primary control parameters, one controlling the relative strength of stochastic noise to the degree of co-alignment and another controlling the degree of the motional bias for those on the edge, relative to the tendency to co-align. We find a novel power-law scaling of the real-space density with the number of individuals N as well as a familiar order-to-disorder transition

A kinetic model describing the processivity of Myosin-V

The precise details of how myosin-V coordinates the biochemical reactions and mechanical motions of its two head elements to engineer effective processive molecular motion along actin filaments remain unresolved. We compare a quantitative kinetic model of the myosin-V walk, consisting of five basic states augmented by two further states to allow for futile hydrolysis and detachments, with experimental results for run lengths, velocities, and dwell times and their dependence on bulk nucleotide concentrations and external loads in both directions. The model reveals how myosin-V can use the internal strain in the molecule to synchronize the motion of the head elements. Estimates for the rate constants in the reaction cycle and the internal strain energy are obtained by a computational comparison scheme involving an extensive exploration of the large parameter space. This scheme exploits the fact that we have obtained analytic results for our reaction network, e.g., for the velocity but also the run length, diffusion constant, and fraction of backward steps. The agreement with experiment is often reasonable but some open problems are highlighted, in particular the inability of such a general model to reproduce the reported dependence of run length on ADP concentration. The novel way that our approach explores parameter space means that any confirmed discrepancies should give new insights into the reaction network model

Measuring Gaussian rigidity using curved substrates

The Gaussian (saddle splay) rigidity of fluid membranes controls their equilibrium topology but is notoriously difficult to measure. In lipid mixtures, typical of living cells, linear interfaces separate liquid ordered (LO) from liquid disordered (LD) bilayer phases at subcritical temperatures. Here we consider such membranes supported by curved supports that thereby control the membrane curvatures. We show how spectral analysis of the fluctuations of the LO-LD interface provides a novel way of measuring the difference in Gaussian rigidity between the two phases. We provide a number of conditions for such interface fluctuations to be both experimentally measurable and sufficiently sensitive to the value of the Gaussian rigidity, whilst remaining in the perturbative regime of our analysis.Comment: 5 pages, 3 figures. v2: version accepted for publicatio

The topological glass in ring polymers

We study the dynamics of concentrated, long, semi-flexible, unknotted and unlinked ring polymers embedded in a gel by Monte Carlo simulation of a coarse-grained model. This involves the ansatz that the rings compactify into a duplex structure where they can be modelled as linear polymers. The classical polymer glass transition involves a rapid loss of microscopic freedom within the polymer molecule as the temperature is reduced toward Tg. Here we are interested in temperatures well above Tg where the polymers retain high microscopic mobility. We analyse the slowing of stress relaxation originating from inter-ring penetrations (threadings). For long polymers an extended network of quasi-topological penetrations forms. The longest relaxation time appears to depend exponentially on the ring polymer contour length, reminiscent of the usual exponential slowing (e.g., with temperature) in classical glasses. Finally, we discuss how this represents a universality class for glassy dynamics

The Role of Projection in the Control of Bird Flocks

Swarming is a conspicuous behavioural trait observed in bird flocks, fish shoals, insect swarms and mammal herds. It is thought to improve collective awareness and offer protection from predators. Many current models involve the hypothesis that information coordinating motion is exchanged between neighbors. We argue that such local interactions alone are insufficient to explain the organization of large flocks of birds and that the mechanism for the exchange of long-ranged information necessary to control their density remains unknown. We show that large flocks self-organize to the maximum density at which a typical individual is still just able to see out of the flock in many directions. Such flocks are marginally opaque - an external observer can also just still see a substantial fraction of sky through the flock. Although seemingly intuitive we show that this need not be the case; flocks could easily be highly diffuse or entirely opaque. The emergence of marginal opacity strongly constrains how individuals interact with each other within large swarms. It also provides a mechanism for global interactions: An individual can respond to the projection of the flock that it sees. This provides for faster information transfer and hence rapid flock dynamics, another advantage over local models. From a behavioural perspective it optimizes the information available to each bird while maintaining the protection of a dense, coherent flock.Comment: PNAS early edition published online at http://www.pnas.org/cgi/doi/10.1073/pnas.140220211