Lorentz Reciprocal Theorem in Fluids with Odd Viscosity.

The Lorentz reciprocal theorem-that is used to study various transport phenomena in hydrodynamics-is violated in chiral active fluids that feature odd viscosity with broken time-reversal and parity symmetries. Here, we show that the theorem can be generalized to fluids with odd viscosity by choosing an auxiliary problem with the opposite sign of the odd viscosity. We demonstrate the application of the theorem to two categories of microswimmers. Swimmers with prescribed surface velocity are not affected by odd viscosity, while those with prescribed active forces are. In particular, a torque dipole can lead to directed motion.

Pair dynamics of active force dipoles in an odd-viscous fluid.

We discuss the lateral dynamics of two active force dipoles, which interact with each other via hydrodynamic interactions in a thin fluid layer that is active and chiral. The fluid layer is modeled as a two-dimensional (2D) compressible fluid with an odd viscosity, while the force dipole (representing an active protein or enzyme) induces a dipolar flow. Taking into account the momentum decay in the 2D fluid, we obtain analytically the mobility tensor that depends on the odd viscosity and includes nonreciprocal hydrodynamic interactions. We find that the particle pair shows spiral behavior due to the transverse flow induced by the odd viscosity. When the magnitude of the odd viscosity is large as compared with the shear viscosity, two types of oscillatory behaviors are seen. One of them can be understood as arising from closed orbits in dynamical systems, and its circular trajectories are determined by the ratio between the magnitude of the odd viscosity and the force dipole. In addition, the phase diagrams of the particle dipolar angles are obtained numerically. Our findings reveal that the nonreciprocal response leads to complex dynamics of active particles embedded in an active fluid with odd viscosity.

Time-correlation functions for odd Langevin systems.

We investigate the statistical properties of fluctuations in active systems that are governed by nonsymmetric responses. Both an underdamped Langevin system with an odd resistance tensor and an overdamped Langevin system with an odd elastic tensor are studied. For a system in thermal equilibrium, the time-correlation functions should satisfy time-reversal symmetry and the antisymmetric parts of the correlation functions should vanish. For the odd Langevin systems, however, we find that the antisymmetric parts of the time-correlation functions can exist and that they are proportional to either the odd resistance coefficient or the odd elastic constant. This means that the time-reversal invariance of the correlation functions is broken due to the presence of odd responses in active systems. Using the short-time asymptotic expressions of the time-correlation functions, one can estimate an odd elastic constant of an active material such as an enzyme or a motor protein.

Nonreciprocal response of a two-dimensional fluid with odd viscosity.

We discuss the linear hydrodynamic response of a two-dimensional active chiral compressible fluid with odd viscosity. The viscosity coefficient represents broken time-reversal and parity symmetries in the 2D fluid and characterizes the deviation of the system from a passive fluid. Taking into account the hydrodynamic coupling to the underlying bulk fluid, we obtain the odd viscosity-dependent mobility tensor, which is responsible for the nonreciprocal hydrodynamic response to a point force. Furthermore, we consider a finite-size disk moving laterally in the 2D fluid and demonstrate that the disk experiences a nondissipative lift force in addition to the dissipative drag one.

Hydrodynamic lift of a two-dimensional liquid domain with odd viscosity.

We discuss hydrodynamic forces acting on a two-dimensional liquid domain that moves laterally within a supported fluid membrane in the presence of odd viscosity. Since active rotating proteins can accumulate inside the domain, we focus on the difference in odd viscosity between the inside and outside of the domain. Taking into account the momentum leakage from a two-dimensional incompressible fluid to the underlying substrate, we analytically obtain the fluid flow induced by the lateral domain motion and calculate the drag and lift forces acting on the moving liquid domain. In contrast to the passive case without odd viscosity, the lateral lift arises in the active case only when the in and out odd viscosities are different. The in-out contrast in the odd viscosity leads to nonreciprocal hydrodynamic responses of an active liquid domain.

Mechanochemical enzymes and protein machines as hydrodynamic force dipoles: the active dimer model.

Mechanochemically active enzymes change their shapes within every turnover cycle. Therefore, they induce circulating flows in the solvent around them and behave as oscillating hydrodynamic force dipoles. Because of non-equilibrium fluctuating flows collectively generated by the enzymes, mixing in the solution and diffusion of passive particles within it are expected to get enhanced. Here, we investigate the intensity and statistical properties of such force dipoles in the minimal active dimer model of a mechanochemical enzyme. In the framework of this model, novel estimates for hydrodynamic collective effects in solution and in lipid bilayers under rapid rotational diffusion are derived, and available experimental and computational data is examined.

Shear viscosity of two-state enzyme solutions.

We discuss the shear viscosity of a Newtonian solution of catalytic enzymes and substrate molecules. The enzyme is modeled as a two-state dimer consisting of two spherical domains connected with an elastic spring. The enzymatic conformational dynamics is induced by the substrate binding and such a process is represented by an additional elastic spring. Employing the Boltzmann distribution weighted by the waiting times of enzymatic species in each catalytic cycle, we obtain the shear viscosity of dilute enzyme solutions as a function of substrate concentration and its physical properties. The substrate affinity distinguishes between fast and slow enzymes, and the corresponding viscosity expressions are obtained. Furthermore, we connect the obtained viscosity with the diffusion coefficient of a tracer particle in enzyme solutions.

Nonequilibrium probability flux of a thermally driven micromachine.

We discuss the nonequilibrium statistical mechanics of a thermally driven micromachine consisting of three spheres and two harmonic springs [Y. Hosaka et al., J. Phys. Soc. Jpn. 86, 113801 (2017)JUPSAU0031-901510.7566/JPSJ.86.113801]. We obtain the nonequilibrium steady state probability distribution function of such a micromachine and calculate its probability flux in the corresponding configuration space. The resulting probability flux can be expressed in terms of a frequency matrix that is used to distinguish between a nonequilibrium steady state and a thermal equilibrium state satisfying detailed balance. The frequency matrix is shown to be proportional to the temperature difference between the spheres. We obtain a linear relation between the eigenvalue of the frequency matrix and the average velocity of a thermally driven micromachine that can undergo a directed motion in a viscous fluid. This relation is consistent with the scallop theorem for a deterministic three-sphere microswimmer.

Three-disk microswimmer in a supported fluid membrane.

A model of three-disk micromachine swimming in a quasi-two-dimensional supported membrane is proposed. We calculate the average swimming velocity as a function of the disk size and the arm length. Due to the presence of the hydrodynamic screening length in the quasi-two-dimensional fluid, the geometric factor appearing in the average velocity exhibits three different asymptotic behaviors depending on the microswimmer size and the hydrodynamic screening length. This is in sharp contrast with a microswimmer in a three-dimensional bulk fluid that shows only a single scaling behavior. We also find that the maximum velocity is obtained when the disks are equal-sized, whereas it is minimized when the average arm lengths are identical. The intrinsic drag of the disks on the substrate does not alter the scaling behaviors of the geometric factor.

Lateral diffusion induced by active proteins in a biomembrane.

We discuss the hydrodynamic collective effects due to active protein molecules that are immersed in lipid bilayer membranes and modeled as stochastic force dipoles. We specifically take into account the presence of the bulk solvent that surrounds the two-dimensional fluid membrane. Two membrane geometries are considered: the free membrane case and the confined membrane case. Using the generalized membrane mobility tensors, we estimate the active diffusion coefficient and the drift velocity as a function of the size of a diffusing object. The hydrodynamic screening lengths distinguish the two asymptotic regimes of these quantities. Furthermore, the competition between the thermal and nonthermal contributions in the total diffusion coefficient is characterized by two length scales corresponding to the two membrane geometries. These characteristic lengths describe the crossover between different asymptotic behaviors when they are larger than the hydrodynamic screening lengths.

PK/PD analysis of biapenem in patients undergoing continuous hemodiafiltration.

BACKGROUND: Continuous hemodiafiltration (CHDF) is used as renal replacement therapy for critically ill patients with renal failure, and to treat hypercytokinemia. Since CHDF also clears therapeutic agents, drug pharmacokinetics (PK) should be dependent upon CHDF conditions. Although the antibiotic biapenem (BIPM) is used in patients undergoing CHDF, the optimal therapeutic regimen in such patients has not been fully clarified. In this study, we investigated the PK of BIPM in patients with various levels of renal function undergoing CHDF with polysulfone (PS) membrane, and used PK models to identify the optimal administration regimen. METHODS: BIPM (300 mg) was administered by infusion in patients undergoing CHDF (n = 7). Blood and filtrate-dialysate were collected for compartment and non-compartment analysis. RESULTS: The sieving coefficient of PS membrane was 1.00 ± 0.06 (mean ± S.D., n = 7), and CHDF clearance of BIPM was found to be the sum of the dialysate flow rate (QD) and filtrate flow rate (QF). Non-CHDF clearance showed inter-individual variability (4.82 ± 2.48 L/h), depending on residual renal function and non-renal clearance. Based on the average PK parameters obtained with a compartmental model, maximal kill end point (over 40 % T > MIC4 µg/mL) was achieved with regimens of 300 mg every 6 h, 300 mg every 8 h, and 600 mg every 12 h. Monte Carlo simulation indicated that 300 mg infusion for 1 h every 6 h was optimal, and the probability of target attainment at MIC2 µg/mL was 90.2 %. CONCLUSIONS: Our results establish the optimal regimen of BIPM in patients with various levels of renal function undergoing CHDF with a PS membrane.