Significance: We custom synthesize a fluorescent ligand and use highly sensitive microscopy methods to show that receptors may be targeted to distinct sites of a cell. We provide microscopic images of the localization of β 1 ‐adrenergic receptors (β 1 -ARs) and β 2 ‐adrenergic receptors (β 2 ‐ARs), main drivers of the contractility of the heart, in heart muscle cells. We show that β 2 ‐ARs are exclusively targeted to specific structures in these cells, the T-tubules, while β 1 -ARs are found at the entire cell surface and in T-tubules. Such differential localization may explain their different physiological functions, even though they trigger the same biochemical signal, i.e. an increase in cyclic adenosine monophosphate (cAMP). Thus, receptor function may be determined not only by their biochemical signals, but also by their specific cellular localization.
We propose an efficient Monte Carlo algorithm for the off-lattice simulation of dense hard sphere polymer melts using cluster moves, called event chains, which allow for a rejection-free treatment of the excluded volume. Event chains also allow for an efficient preparation of initial configurations in polymer melts. We parallelize the event chain Monte Carlo algorithm to further increase simulation speeds and suggest additional local topology-changing moves (“swap” moves) to accelerate equilibration. By comparison with other Monte Carlo and molecular dynamics simulations, we verify that the event chain algorithm reproduces the correct equilibrium behavior of polymer chains in the melt. By comparing intrapolymer diffusion time scales, we show that event chain Monte Carlo algorithms can achieve simulation speeds comparable to optimized molecular dynamics simulations. The event chain Monte Carlo algorithm exhibits Rouse dynamics on short time scales. In the absence of swap moves, we find reptation dynamics on intermediate time scales for long chains.
Soft elastic capsules which are driven through a viscous fluid undergo shape deformation coupled to their motion. We introduce an iterative solution scheme which couples hydrodynamic boundary integral methods and elastic shape equations to find the stationary axisymmetric shape and the velocity of an elastic capsule moving in a viscous fluid at low Reynolds numbers. We use this approach to systematically study dynamical shape transitions of capsules with Hookean stretching and bending energies and spherical rest shape sedimenting under the influence of gravity or centrifugal forces. We find three types of possible axisymmetric stationary shapes for sedimenting capsules with fixed volume: a pseudospherical state, a pear-shaped state, and buckled shapes. Capsule shapes are controlled by two dimensionless parameters, the Föppl-von-Kármán number characterizing the elastic properties and a Bond number characterizing the driving force. For increasing gravitational force the spherical shape transforms into a pear shape. For very large bending rigidity (very small Föppl-von-Kármán number) this transition is discontinuous with shape hysteresis. The corresponding transition line terminates, however, in a critical point, such that the discontinuous transition is not present at typical Föppl-von-Kármán numbers of synthetic capsules. In an additional bifurcation, buckled shapes occur upon increasing the gravitational force. This type of instability should be observable for generic synthetic capsules. All shape bifurcations can be resolved in the force-velocity relation of sedimenting capsules, where up to three capsule shapes with different velocities can occur for the same driving force. All three types of possible axisymmetric stationary shapes are stable with respect to rotation during sedimentation. Additionally, we study capsules pushed or pulled by a point force, where we always find capsule shapes to transform smoothly without bifurcations.
We present the results from kinetic theory for a system of self-propelled particles with alignment interactions of higher-order symmetry, particularly nematic ones. To this end, we use the Landau equation approach, a systematic approximation to the BBGKY hierarchy for small effective couplings. Our calculations are presented in a pedagogical way with the explicit goal of serving as a tutorial from a physicists’ perspective into applying kinetic theory ideas beyond mean-field to active matter systems with essentially no prerequisites and yield predictions without free parameters that are in quantitative agreement with direct agent-based simulations
Spatiotemporal signal shaping in G protein-coupled receptor (GPCR) signaling is now a well-established and accepted notion to explain how signaling specificity can be achieved by a superfamily sharing only a handful of downstream second messengers. Dozens of G-coupled GPCR signals ultimately converge on the production of cAMP, a ubiquitous second messenger. This idea is almost always framed in terms of local concentrations, the differences in which are maintained by means of spatial separation. However, given the dynamic nature of the reaction-diffusion processes at hand, the dynamics, in particular the local diffusional properties of the receptors and their cognate G proteins, are also important. By combining some first principle considerations, simulated data, and experimental data of the receptors diffusing on the membranes of living cells, we offer a short perspective on the modulatory role of local membrane diffusion in regulating GPCR-mediated cell signaling. Our analysis points to a diffusion-limited regime where the effective production rate of activated G protein scales linearly with the receptor–G protein complex’s relative diffusion rate and to an interesting role played by the membrane geometry in modulating the efficiency of coupling.