A continuum treatment of growth in biological tissue: The coupling of mass transport and mechanics

Growth (and resorption) of biological tissue is formulated in the continuum setting. The treatment is macroscopic, rather than cellular or sub-cellular. Certain assumptions that are central to classical continuum mechanics are revisited, the theory is reformulated, and consequences for balance laws and constitutive relations are deduced. The treatment incorporates multiple species. Sources and fluxes of mass, and terms for momentum and energy transfer between species are introduced to enhance the classical balance laws. The transported species include: (\romannumeral 1) a fluid phase, and (\romannumeral 2) the precursors and byproducts of the reactions that create and break down tissue. A notable feature is that the full extent of coupling between mass transport and mechanics emerges from the thermodynamics. Contributions to fluxes from the concentration gradient, chemical potential gradient, stress gradient, body force and inertia have not emerged in a unified fashion from previous formulations of the problem. The present work demonstrates these effects via a physically-consistent treatment. The presence of multiple, interacting species requires that the formulation be consistent with mixture theory. This requirement has far-reaching consequences. A preliminary numerical example is included to demonstrate some aspects of the coupled formulation.Comment: 29 pages, 11 figures, accepted for publication in Journal of the Mechanics and Physics of Solids. See journal for final versio

Stokesian Dynamics

Particles suspended or dispersed in a fluid medium occur in a wide variety of natural and man-made settings, e.g. slurries, composite materials, ceramics, colloids, polymers, proteins, etc. The central theoretical and practical problem is to understand and predict the macroscopic equilibrium and transport properties of these multiphase materials from their microstructural mechanics. The macroscopic properties might be the sedimentation or aggregation rate, self-diffusion coefficient, thermal conductivity, or rheology of a suspension of particles. The microstructural mechanics entails the Brownian, interparticle, external, and hydrodynamic forces acting on the particles, as well as their spatial and temporal distribution, which is commonly referred to as the microstructure. If the distribution of particles were given, as well as the location and motion of any boundaries and the physical properties of the particles and suspending fluid, one would simply have to solve (in principle, not necessarily in practice) a well-posed boundary-value problem to determine the behavior of the material. Averaging this solution over a large volume or over many different configurations, the macroscopic or averaged properties could be determined. The two key steps in this approach, the solution of the many-body problem and the determination of the microstructure, are formidable but essential tasks for understanding suspension behavior. This article discusses a new, molecular-dynamics-like approach, which we have named Stokesian dynamics, for dynamically simulating the behavior of many particles suspended or dispersed in a fluid medium. Particles in suspension may interact through both hydrodynamic and nonhydrodynamic forces, where the latter may be any type of Brownian, colloidal, interparticle, or external force. The simulation method is capable of predicting both static (i.e. configuration-specific) and dynamic microstructural properties, as well as macroscopic properties in either dilute or concentrated systems. Applications of Stokesian dynamics are widespread; problems of sedimentation, flocculation, diffusion, polymer rheology, and transport in porous media all fall within its domain. Stokesian dynamics is designed to provide the same theoretical and computational basis for multiphase, dispersed systems as does molecular dynamics for statistical theories of matter. This review focuses on the simulation method, not on the areas in which Stokesian dynamics can be used. For a discussion of some of these many different areas, the reader is referred to the excellent reviews and proceedings of topical conferences that have appeared (e.g. Batchelor 1976a, Dickinson 1983, Faraday Discussions 1983, 1987, Family & Landau 1984). Before embarking on a description of Stokesian dynamics, we pause here to discuss some of the relevant theoretical literature on suspensions, and dynamic simulation in general, in order to put Stokesian dynamics in perspective

A Continuum Poisson-Boltzmann Model for Membrane Channel Proteins

Membrane proteins constitute a large portion of the human proteome and perform a variety of important functions as membrane receptors, transport proteins, enzymes, signaling proteins, and more. The computational studies of membrane proteins are usually much more complicated than those of globular proteins. Here we propose a new continuum model for Poisson-Boltzmann calculations of membrane channel proteins. Major improvements over the existing continuum slab model are as follows: 1) The location and thickness of the slab model are fine-tuned based on explicit-solvent MD simulations. 2) The highly different accessibility in the membrane and water regions are addressed with a two-step, two-probe grid labeling procedure, and 3) The water pores/channels are automatically identified. The new continuum membrane model is optimized (by adjusting the membrane probe, as well as the slab thickness and center) to best reproduce the distributions of buried water molecules in the membrane region as sampled in explicit water simulations. Our optimization also shows that the widely adopted water probe of 1.4 {\AA} for globular proteins is a very reasonable default value for membrane protein simulations. It gives an overall minimum number of inconsistencies between the continuum and explicit representations of water distributions in membrane channel proteins, at least in the water accessible pore/channel regions that we focus on. Finally, we validate the new membrane model by carrying out binding affinity calculations for a potassium channel, and we observe a good agreement with experiment results.Comment: 40 pages, 6 figures, 5 table

Dynamics of Current, Charge and Mass

Electricity plays a special role in our lives and life. Equations of electron dynamics are nearly exact and apply from nuclear particles to stars. These Maxwell equations include a special term the displacement current (of vacuum). Displacement current allows electrical signals to propagate through space. Displacement current guarantees that current is exactly conserved from inside atoms to between stars, as long as current is defined as Maxwell did, as the entire source of the curl of the magnetic field. We show how the Bohm formulation of quantum mechanics allows easy definition of current. We show how conservation of current can be derived without mention of the polarization or dielectric properties of matter. Matter does not behave the way physicists of the 1800's thought it does with a single dielectric constant, a real positive number independent of everything. Charge moves in enormously complicated ways that cannot be described in that way, when studied on time scales important today for electronic technology and molecular biology. Life occurs in ionic solutions in which charge moves in response to forces not mentioned or described in the Maxwell equations, like convection and diffusion. Classical derivations of conservation of current involve classical treatments of dielectrics and polarization in nearly every textbook. Because real dielectrics do not behave in a classical way, classical derivations of conservation of current are often distrusted or even ignored. We show that current is conserved exactly in any material no matter how complex the dielectric, polarization or conduction currents are. We believe models, simulations, and computations should conserve current on all scales, as accurately as possible, because physics conserves current that way. We believe models will be much more successful if they conserve current at every level of resolution, the way physics does.Comment: Version 4 slight reformattin

Structure-function mapping of a heptameric module in the nuclear pore complex.

The nuclear pore complex (NPC) is a multiprotein assembly that serves as the sole mediator of nucleocytoplasmic exchange in eukaryotic cells. In this paper, we use an integrative approach to determine the structure of an essential component of the yeast NPC, the ~600-kD heptameric Nup84 complex, to a precision of ~1.5 nm. The configuration of the subunit structures was determined by satisfaction of spatial restraints derived from a diverse set of negative-stain electron microscopy and protein domain-mapping data. Phenotypic data were mapped onto the complex, allowing us to identify regions that stabilize the NPC's interaction with the nuclear envelope membrane and connect the complex to the rest of the NPC. Our data allow us to suggest how the Nup84 complex is assembled into the NPC and propose a scenario for the evolution of the Nup84 complex through a series of gene duplication and loss events. This work demonstrates that integrative approaches based on low-resolution data of sufficient quality can generate functionally informative structures at intermediate resolution