Charles S. Peskin

The immersed boundary method

This paper is concerned with the mathematical structure of the immersed boundary (IB) method, which is intended for the computer simulation of fluid–structure interaction, especially in biological fluid dynamics. The IB formulation of such problems, derived here from the principle of least action, involves both Eulerian and Lagrangian variables, linked by the Dirac delta function. Spatial discretization of the IB equations is based on a fixed Cartesian mesh for the Eulerian variables, and a moving curvilinear mesh for the Lagrangian variables. The two types of variables are linked by interaction equations that involve a smoothed approximation to the Dirac delta function. Eulerian/Lagrangian identities govern the transfer of data from one mesh to the other. Temporal discretization is by a second-order Runge–Kutta method. Current and future research directions are pointed out, and applications of the IB method are briefly discussed.

Numerical analysis of blood flow in the heart

Abstract The flow pattern of blood in the heart is intimately connected with the performance of the heart valves. This paper extends previous work on the solution of the Navier-Stokes equations in the presence of moving immersed boundaries which interact with the fluid. The boundary representation now includes the muscular heart wall. The fixed topology of the boundary representation is exploited in the solution of the nonlinear equations which implicitly define the boundary forces. An improved numerical representation of the δ-function is introduced. A fast Laplace-solver is used. The results of calculations with a natural valve and with a prosthetic valve are presented.

Flow patterns around heart valves: A numerical method

Abstract The subject of this paper is the flow of a viscous incompressible fluid in a region containing immersed boundaries which move with the fluid and exert forces on the fluid. An example of such a boundary is the flexible leaflet of a human heart valve. It is the main achievement of the present paper that a method for solving the Navier-Stokes equations on a rectangular domain can now be applied to a problem involving this type of immersed boundary. This is accomplished by replacing the boundary by a field of force which is defined on the mesh points of the rectangular domain and which is calculated from the configuration of the boundary. In order to link the representations of the boundary and fluid, since boundary points and mesh points need not coincide, a semi-discrete analog of the δ function is introduced. Because the boundary forces are of order h −1 , and because they are sensitive to small changes in boundary configuration, they tend to produce numerical instability. This difficulty is overcome by an implicit method for calculating the boundary forces, a method which takes into account the displacements that will be produced by the boundary forces themselves. The numerical scheme is applied to the two-dimensional simulation of flow around the natural mitral valve.

Stochastic mRNA Synthesis in Mammalian Cells

Individual cells in genetically homogeneous populations have been found to express different numbers of molecules of specific proteins. We investigated the origins of these variations in mammalian cells by counting individual molecules of mRNA produced from a reporter gene that was stably integrated into the cells genome. We found that there are massive variations in the number of mRNA molecules present in each cell. These variations occur because mRNAs are synthesized in short but intense bursts of transcription beginning when the gene transitions from an inactive to an active state and ending when they transition back to the inactive state. We show that these transitions are intrinsically random and not due to global, extrinsic factors such as the levels of transcriptional activators. Moreover, the gene activation causes burst-like expression of all genes within a wider genomic locus. We further found that bursts are also exhibited in the synthesis of natural genes. The bursts of mRNA expression can be buffered at the protein level by slow protein degradation rates. A stochastic model of gene activation and inactivation was developed to explain the statistical properties of the bursts. The model showed that increasing the level of transcription factors increases the average size of the bursts rather than their frequency. These results demonstrate that gene expression in mammalian cells is subject to large, intrinsically random fluctuations and raise questions about how cells are able to function in the face of such noise.

Cellular motions and thermal fluctuations: the Brownian ratchet

We present here a model for how chemical reactions generate protrusive forces by rectifying Brownian motion. This sort of energy transduction drives a number of intracellular processes, including filopodial protrusion, propulsion of the bacterium Listeria, and protein translocation.

Numerical Simulation and Experimental Validation of Blood Flow in Arteries with Structured-Tree Outflow Conditions

AbstractBlood flow in the large systemic arteries is modeled using one-dimensional equations derived from the axisymmetric Navier–Stokes equations for flow in compliant and tapering vessels. The arterial tree is truncated after the first few generations of large arteries with the remaining small arteries and arterioles providing outflow boundary conditions for the large arteries. By modeling the small arteries and arterioles as a structured tree, a semi-analytical approach based on a linearized version of the governing equations can be used to derive an expression for the root impedance of the structured tree in the frequency domain. In the time domain, this provides the proper outflow boundary condition. The structured tree is a binary asymmetric tree in which the radii of the daughter vessels are scaled linearly with the radius of the parent vessel. Blood flow and pressure in the large vessels are computed as functions of time and axial distance within each of the arteries. Comparison between the simulations and magnetic resonance measurements in the ascending aorta and nine peripheral locations in one individual shows excellent agreement between the two.

A three-dimensional computational method for blood flow in the heart. 1. Immersed elastic fibers in a viscous incompressible fluid

Abstract This paper describes the numerical solution of the 3-dimensional equations of motion of a viscous incompressible fluid that contains an immersed system of elastic fibers. Implementation details such as vectorization and the efficient use of external memory are discussed. The method is applied to the damped vibrations of a fiber-wound toroidal tube, and empirical evidence of convergence is presented.

A detailed predictive model of the mammalian circadian clock

Experimental data on the circadian (≈24-h) clock in mammalian cells are vast, diverse, and detailed. Mathematical models are therefore needed to piece these data together and to study overall clock behavior. Previous models have focused on Neurospora or Drosophila or can be converted to a Drosophila model simply by renaming variables. Those models used Hill-type terms for transcription regulation and Michaelis–Menten type or delay terms for posttranslation regulation. Recent mammalian experimental data call into question some of the assumptions in these approaches. Moreover, gene duplication has led to more proteins in the mammalian system than in lower organisms. Here we develop a detailed distinctly mammalian model by using mass action kinetics. Parameters for our model are found from experimental data by using a coordinate search method. The model accurately predicts the phase of entrainment, amplitude of oscillation, and shape of time profiles of clock mRNAs and proteins and is also robust to parameter changes and mutations.

A computational model of aquatic animal locomotion

Abstract A computational model of the swimming of a neutrally buoyant organism undergoing deformations within a region of fluid is presented. The fluid is regarded as viscous and incompressible and the organism as a massless, elastic boundary immersed in this fluid. Fluid quantities are represented on a grid (Eulerian description), and the immersed boundary is represented by a discrete collection of moving points (Lagrangian description). Computed results are presented, along with comparisons with previous asymptotic analysis.

An adaptive, formally second order accurate version of the immersed boundary method

Like many problems in biofluid mechanics, cardiac mechanics can be modeled as the dynamic interaction of a viscous incompressible fluid (the blood) and a (visco-)elastic structure (the muscular walls and the valves of the heart). The immersed boundary method is a mathematical formulation and numerical approach to such problems that was originally introduced to study blood flow through heart valves, and extensions of this work have yielded a three-dimensional model of the heart and great vessels. In the present work, we introduce a new adaptive version of the immersed boundary method. This adaptive scheme employs the same hierarchical structured grid approach (but a different numerical scheme) as the two-dimensional adaptive immersed boundary method of Roma et al. [A multilevel self adaptive version of the immersed boundary method, Ph.D. Thesis, Courant Institute of Mathematical Sciences, New York University, 1996; An adaptive version of the immersed boundary method, J. Comput. Phys. 153 (2) (1999) 509–534] and is based on a formally second order accurate (i.e., second order accurate for problems with sufficiently smooth solutions) version of the immersed boundary method that we have recently described [B.E. Griffith, C.S. Peskin, On the order of accuracy of the immersed boundary method: higher order convergence rates for sufficiently smooth problems, J. Comput. Phys. 208 (1) (2005) 75–105]. Actual second order convergence rates are obtained for both the uniform and adaptive methods by considering the interaction of a viscous incompressible flow and an anisotropic incompressible viscoelastic shell. We also present initial results from the application of this methodology to the three-dimensional simulation of blood flow in the heart and great vessels. The results obtained by the adaptive method show good qualitative agreement with simulation results obtained by earlier non-adaptive versions of the method, but the flow in the vicinity of the model heart valves indicates that the new methodology provides enhanced boundary layer resolution. Differences are also observed in the flow about the mitral valve leaflets.