Internal organs are asymmetrically positioned inside the body. Embryonic motile cilia play an essential role in this process by generating a directional fluid flow inside the vertebrate left-right organizer. Detailed characterization of how fluid flow dynamics modulates laterality is lacking. We used zebrafish genetics to experimentally generate a range of flow dynamics. By following the development of each embryo, we show that fluid flow in the left-right organizer is asymmetric and provides a good predictor of organ laterality. This was tested in mosaic organizers composed of motile and immotile cilia generated by dnah7 knockdowns. In parallel, we used simulations of fluid dynamics to analyze our experimental data. These revealed that fluid flow generated by 30 or more cilia predicts 90% situs solitus, similar to experimental observations. We conclude that cilia number, dorsal anterior motile cilia clustering, and left flow are critical to situs solitus via robust asymmetric charon expression.

Isotropic phoretic particles do not swim individually but can achieve self-propulsion collectively by spontaneously forming clusters of anisotropic geometry.

Shear-thinning is an important rheological property of many biological fluids, such as mucus, whereby the apparent viscosity of the fluid decreases with shear. Certain microscopic swimmers have been shown to progress more rapidly through shear-thinning fluids, but is this behavior generic to all microscopic swimmers, and what are the physics through which shear-thinning rheology affects a swimmer's propulsion? We examine swimmers employing prescribed stroke kinematics in two-dimensional, inertialess Carreau fluid: shear-thinning "Generalized Stokes" flow. Swimmers are modeled, using the method of femlets, by a set of immersed, regularized forces. The equations governing the fluid dynamics are then discretized over a bodyfitted mesh and solved with the finite element method. We analyze the locomotion of three distinct classes of microswimmer: (1) conceptual swimmers comprising sliding spheres employing both one-and two-dimensional strokes, (2) slip-velocity envelope models of ciliates commonly referred to as "squirmers" and (3) monoflagellate pushers, such as sperm. We find that morphologically identical swimmers with different strokes may swim either faster or slower in shear-thinning fluids than in Newtonian fluids. We explain this kinematic sensitivity by considering differences in the viscosity of the fluid surrounding propulsive and payload elements of the swimmer, and using this insight suggest two reciprocal sliding sphere swimmers which violate Purcell's Scallop theorem in shear-thinning fluids. We also show that an increased flow decay rate arising from shear-thinning rheology is associated with a reduction in the swimming speed of slip-velocity squirmers. For sperm-like swimmers, a gradient of thick to thin fluid along the flagellum alters the force it exerts upon the fluid, flattening trajectories and increasing instantaneous swimming speed. Montenegro-Johnson et al., Phys. Fluids 25, 081903 (2013); http://dx.

Diverse molecular networks underlying plant growth and development are rapidly being uncovered. Integrating these data into the spatial and temporal context of dynamic organ growth remains a technical challenge. We developed 3DCellAtlas, an integrative computational pipeline that semiautomatically identifies cell types and quantifies both 3D cellular anisotropy and reporter abundance at single-cell resolution across whole plant organs. Cell identification is no less than 97.8% accurate and does not require transgenic lineage markers or reference atlases. Cell positions within organs are defined using an internal indexing system generating cellular level organ atlases where data from multiple samples can be integrated. Using this approach, we quantified the organ-wide cell-type-specific 3D cellular anisotropy driving Arabidopsis thaliana hypocotyl elongation. The impact ethylene has on hypocotyl 3D cell anisotropy identified the preferential growth of endodermis in response to this hormone. The spatiotemporal dynamics of the endogenous DELLA protein RGA, expansin gene EXPA3, and cell expansion was quantified within distinct cell types of Arabidopsis roots. A significant regulatory relationship between RGA, EXPA3, and growth was present in the epidermis and endodermis. The use of single-cell analyses of plant development enables the dynamics of diverse regulatory networks to be integrated with 3D organ growth.

Cilia and flagella are actively bending slender organelles, performing functions such as motility, feeding and embryonic symmetry breaking. We review the mechanics of viscous-dominated microscale flow, including time-reversal symmetry, drag anisotropy of slender bodies, and wall effects. We focus on the fundamental force singularity, higher order multipoles, and the method of images, providing physical insight and forming a basis for computational approaches. Two biological problems are then considered in more detail: (1) left-right symmetry breaking flow in the node, a microscopic structure in developing vertebrate embryos, and (2) motility of microswimmers through non-Newtonian fluids. Our model of the embryonic node reveals how particle transport associated with morphogenesis is modulated by the gradual emergence of cilium posterior tilt. Our model of swimming makes use of force distributions within a body-conforming finite element framework, allowing the solution of nonlinear inertialess Carreau flow. We find that a threesphere model swimmer and a model sperm are similarly affected by shear-thinning; in both cases swimming due to a prescribed beat is enhanced by shear-thinning, with optimal Deborah number around 0.8. The sperm exhibits an almost perfect linear relationship between velocity and the logarithm of the ratio of zero to infinite shear viscosity, with shear-thickening hindering cell progress. Montenegro-Johnson et al, Eur. Phys. J. E, 35 10 (

Through billions of years of evolution, microorganisms mastered unique swimming behaviors to thrive in complex fluid environments. Limitations in nanofabrication have thus far hindered the ability to design and program synthetic swimmers with the same abilities. Here we encode multi-behavioral responses in microscopic self-propelled tori using nanoscale 3D printing. We show experimentally and theoretically that the tori continuously transition between two primary swimming modes in response to a magnetic field. The tori also manipulated and transported other artificial swimmers, bimetallic nanorods, as well as passive colloidal particles. In the first behavioral mode, the tori accumulated and transported nanorods; in the second mode, nanorods aligned along the toriʼs self-generated streamlines. Our results indicate that such shape-programmed microswimmers have a potential to manipulate biological active matter, e.g. bacteria or cells.

Abstract. An efficient, accurate, and flexible numerical method is proposed for the solution of the swimming problem of one or more autophoretic particles in the purely-diffusive limit. The method relies on successive boundary element solutions of the Laplacian and the Stokes flow equations using regularised Green's functions for swift, simple implementations, an extension of the well-known method of "regularised stokeslets" for Stokes flow problems. The boundary element method is particularly suitable for phoretic problems, since no quantities in the domain bulk are required to compute the swimming velocity. For time-dependent problems, the method requires no re-meshing and simple boundaries such as a plane wall may be added at no increase to the size of the linear system through the method of images. The method is validated against two classical examples for which an analytical or semi-analytical solution is known, a two-sphere system and a Janus particle, and provides a rigorous computational pipeline to address further problems with complex geometry and multiple bodies.

The dynamics of geometrically non-linear flexible filaments play an important role in a host of biological processes, from flagella-driven cell transport to the polymeric structure of complex fluids. Such problems have historically been computationally expensive due to numerical stiffness associated with the inextensibility constraint, as well as the often non-trivial boundary conditions on the governing high-order PDEs. Formulating the problem for the evolving shape of a filament via an integral equation in the tangent angle has recently been found to greatly alleviate this numerical stiffness. The contribution of the present manuscript is to enable the simulation of nonlocal interactions of multiple filaments in a computationally efficient manner using the method of regularized stokeslets within this framework. The proposed method is benchmarked against a nonlocal bead and link model, and recent code utilizing a local drag velocity law. Systems of multiple filaments (1) in a background fluid flow, (2) under a constant body force, and (3) undergoing active self-motility are modeled efficiently. Buckling instabilities are analyzed by examining the evolving filament curvature, as well as by coarse-graining the body frame tangent angles using a Chebyshev approximation for various choices of the relevant non-dimensional parameters. From these experiments, insight is gained into how filament-filament interactions can promote buckling, and further reveal the complex fluid dynamics resulting from arrays of these interacting fibers. By examining active moment-driven filaments, we investigate the speed of worm-and sperm-like swimmers for different governing parameters. The MATLAB R implementation is made available as an open-source library, enabling flexible extension for alternate discretizations and different surrounding flows.