CTW: Mathematical and Computational Challenges in Cilia- and Flagella-Induced Fluid Dynamics
(October 15,2012 - October 18,2012 )
Organizers
Cilia and flagella are ubiquitous in cell biology, acting either in a coordinated fashion to move surrounding fluid such as in lung airways, or as a propeller for cell locomotion such as on sperm or eukaryotic microorganisms, or as a sensory immotile but flexible antenna such as the primary cilia in essentially every cell in vertebrates and many vertebrate and invertebrate sense organs. The fluid dynamics induced by cilia and flagella, the mechanisms of coordination of motile cilia and flagella, and the fluid dynamic feedback to intra-ciliary and intra-flagellar transport and signaling, are essential to biology. The purpose of this workshop is to convene experts in biology, physics, mathematical modeling, and scientific computation to collectively assess progress and identify challenges to be undertaken in cilia- and flagella-induced fluid dynamics. A list of outstanding challenges and computational strategies will be highlighted through lectures and subsequent discussions and open forums: (i) methods to compute and resolve the fluid-structure interaction of a cilium or flagellum, in either a viscous or viscoelastic fluid; (ii) stochastic (based on molecular motors) versus deterministic coarse-grained models of cilia and flagella beat cycles; (iii) the coordination mechanisms of cilia and flagella through the intervening fluid and/or the cells they emanate from; (iv) fluid mechanical sensing by the cilium or flagellum and the feedback response; (v) fundamental questions of optimization and efficiency (tuning of ciliary or flagellar motion or tuning of fluid properties to optimize motility or fluid transport; (vi) experimental and engineering approaches to support and challenge new modeling approaches. These challenges require assessment of current formulations and analysis of the governing equations for existing models, attention to accuracy, stiffness, time-stepping, adaptive mesh refinement, parallel implementation, and computing architectures.
Accepted Speakers
Martina Brueckner
Pediatrics and Genetics, Yale University
Ricardo Cortez
Mathematics Dept., Tulane University
William Davis
Cystic Fibrosis/Pulmonary Research & Treatment Center, University of North Carolina, Chapel Hill
Robert Dillon
Department of Mathematics, Washington State University
Zvonimir Dogic
Physics, Brandeis University
Lisa Fauci
Mathematics, Tulane University
Marc Fermigier
Physics, ESPCI
Guilherme Garcia
Biotechnology and Bioengineering Center, Medical College of Wisconsin
Ambarish Ghosh
Indian Institute of Science, Bangalore
Ramin Golestanian
Physics, University of Oxford
Kent Hill
MIMG, University of Southern California
Steve King
Molecular Microbial and Structural Biology, University of Connecticut Health Center
Karl Lechtreck
Cellular Biology, University of Georgia
Karin Leiderman
Applied Mathematics, University of California Merced
Sorin Mitran
Mathematics, University of North Carolina, Chapel Hill
Chris O'Callaghan
Paediatrics, University of Leicester
Sarah Olson
Department of Mathematical Sciences, Worcester Polytechnic Institute
Helle Praetorius
Dept. of Biomedicine (physiology), Aarhus University
Winfield Sale
Cell Biology, Emory University
Michael Shelley
The Courant Institute, New York University
Saverio Spagnolie
Mathematics, University of Wisconsin
Anna-Karin Tornberg
Numerical Analysis, KTH - Royal Institute of Technology
| Monday, October 15, 2012 | |
|---|---|
| Time | Session |
| 08:00 AM | Shuttle to MBI |
| 08:15 AM 08:45 AM | Breakfast |
| 08:45 AM 09:00 AM | Welcome, overview of workshop, and introductions: Marty Golubitsky |
| 09:00 AM 09:45 AM | Martina Brueckner - Cilia in the Development of Left-right asymmetry Cilia in the Development of Left-right asymmetry |
| 09:45 AM 09:55 AM | Q & A |
| 09:55 AM 10:25 AM | Helle Praetorius - ---and everything will flow Primary cilia are able to sense flow. This is these years a banality � or is it? The question has been addressed with quite many approaches. And at least for a long row of mechano-sensitive cells, especially epithelial cells with long cilia this seem to hold. The primary cilium is not in itself necessary for a cell to be mechano-sensitive. If the stimulus were substantial enough any cell would react to mechanical stimulation. The cilium merely sensitise a given cell to mechanical stimuli � and that gives a challenge when one wants to address the ciliary effects. First of all they are subtle, which means that one has to titrate the system to catch these effects without mechanically over-stimulating the cells. Nevertheless, when addressing the sensory functions of cilia, mechanical or receptory � less is more. The talk is a short overview over the cilum as a flow censor and how to catch the signal. |
| 10:25 AM 10:30 AM | Q & A |
| 10:30 AM 11:00 AM | Break |
| 11:00 AM 11:30 AM | Blitz session (Three 10-minute talks): Steve King, Karl Lechtreck, and Kent Hill |
| 11:00 AM 11:10 AM | Steve King - Planarians as a Genetically Tractable Model for a Ciliated Epithelium The planarian ventral surface is a completely exposed ciliated epithelium. These animals utilize their motile cilia to generate gliding locomotion by beating against secreted mucus. The ventral cilia have a standard 9+2 axoneme containing both inner and outer rows of dynein arms and beat at ~22 Hz. RNAi knockdown approaches are simple and robust, leading to reductions in mRNA to almost undetectable levels. Thus, planaria may be used to rapidly screen proteins of unknown function for their role in ciliary assembly and/or motility, and may also provide a useful model system in which to investigate muco-ciliary interactions. I will discuss the use of this organism to analyze the role of outer arm dynein components in generating motile force and in maintaining the hydrodynamic coupling required for metachronal synchrony of beating cilia. |
| 11:10 AM 11:20 AM | Karl Lechtreck - Ciliary Motility- outside and inside The ventricular system in the brain is lined by multiciliated cells. The motility of these ependymal cilia was analyzed in hy3-/- mice which carry a null mutation in Hydin and develop lethal hydrocephalus. Hy3-/- cilia lack a projection from the ciliary central pair and move with slightly reduced beat frequency and a greatly reduced beat amplitude. They lack the ability to generate fluid flow explaining the hydrocephalic phenotype of the mutant mice. The assembly of motile and non-motile cilia requires intraflagellar transport (IFT) but it remains largely unknown how IFT traffics ciliary precursors. Simultaneous in vivo imaging of IFT and cargoes revealed a complex pattern of IFT and non-IFT cargo movements, and unloading and assembly site docking events. Quantitative data on cargo frequency, assembly, and turn-over will provide a basis for future modeling of ciliary assembly and dynamics. |
| 11:30 AM 12:30 PM | Panel-led discussion |
| 12:30 PM 02:00 PM | Lunch Break |
| 02:00 PM 02:45 PM | Marc Fermigier - Engineered microswimmers and micropumps Since the pioneering studies of GI Taylor in the fifties, models have been used to gain understanding in the propulsion of microorganisms. Modern microfabrication techniques enable us to assemble very small scale devices emulating the motion of cilia. I will review the different strategies used in recent years towards the goal of fabricating micron scale artificial swimmers. In particular I will discuss the relative merits of self-assembly and micromolding. I will describle several sources of propulsive energy but most of the talk will be devoted to magnetically driven systems. |
| 02:45 PM 02:55 PM | Q & A |
| 02:55 PM 03:25 PM | Ambarish Ghosh - Magnetically actuated helical nanostructures Maneuvering nanoscale objects in fluidic media in a non-invasive manner can lead to various biomedical applications, and is pursued by researchers across many disciplines. Of particular interest is the possibility of powering and controlling the motion of nanoscale objects with small, homogeneous magnetic fields, which is easy to achieve, and guaranteed to be non-invasive as well. This has recently been achieved by various groups using advanced nanofabrication techniques, where magnetic nanoscale objects of different shapes, such as helical, flexible rod-likeetc. have been maneuvered in a controllable fashion using either rotating or undulating magnetic fields. In particular, cork-screw motion is achieved in ferromagnetic helical nanostructures by aligning the permanent magnetic moments of the helix with a rotating magnetic field, causing the nanostructure to rotate and therefore propel. Such systems have been referred to as either magnetic nanopropellers or as artificial bacterial flagella in the literature. In this talk, we will discuss the fabrication and actuation of such a system, and describe their complex dynamical behavior in the presence of thermal fluctuations. In particular, we will describe how this novel system can show bistable dynamics and may have non-gaussian speed fluctuations under certain conditions. |
| 03:25 PM 03:30 PM | Q & A |
| 03:30 PM 04:00 PM | Break |
| 04:00 PM 04:10 PM | Rich Superfine - Afternoon Blitz Session Talk (10-15-2012) (Rich Superfine) Blitz Session Talk (Rich Superfine) |
| 04:00 PM 04:30 PM | Blitz session (Three 10-minute talks) |
| 04:10 PM 04:20 PM | Arezoo Ardekan - Afternoon Blitz Session Talk (10-15-2012) (Arezoo Ardekani) Blitz Session (Arezoo Ardekani) |
| 04:20 PM 04:30 PM | Ramin Golestanian - Afternoon Blitz Session Talk (10-15-2012) (Ramin Golestanian) Blitz Session (Ramin Glestanian) |
| 04:30 PM 05:30 PM | Panel-led discussion |
| 04:30 PM 04:40 PM | Kenny Breuer - Afternoon Blitz Session Talk (10-15-2012) (Kenny Breuer) Afternoon Blitz Session Talk (10-15-2012) (Kenny Breuer) |
| 05:30 PM 07:00 PM | Reception and poster session in MBI Lounge |
| 07:00 PM | Shuttle pick-up from MBI |
| Tuesday, October 16, 2012 | |
|---|---|
| Time | Session |
| 08:15 AM | Shuttle to MBI |
| 08:45 AM 09:00 AM | Breakfast |
| 09:00 AM 09:45 AM | Lisa Fauci - Computational models of ciliary dynamics: successes and challenges The beating of a cilium is an elegant example of an actuated elastic structure coupled to a surrounding fluid. Computational fluid dynamics enthusiasts will recognize that ciliary systems present many complications such as the interaction of groups of cilia, the influence of boundaries, and the coupling to fluids that have complex rheology and microstructures. Moreover, the ciliary beatform is an emergent feature of these mechanical considerations along with biochemical processes. We will present an overview of current CFD models of cilia, along with some recent progress in analyzing fluid mixing by cilia and modeling ciliary penetration of a mucus layer. |
| 09:45 AM 09:55 AM | Question and Answer |
| 09:55 AM 10:25 AM | Ricardo Cortez - Slender body theory using regularized Stokeslets Slender-body theories allow for the representation of thin tubes in Stokes' flow by a distribution of fundamental solutions along the filament center line while approximately enforcing boundary conditions on the surface of the tube. The idea is revisited here in the more general setting of regularized forces in a small neighborhood of the center line. The regularity in the forces produces a smooth final expression that helps eliminate the computational instabilities of the unregularized formulas. The derivations of the regular slender body theories corresponding with the standard theories of Lighthill and of Keller and Rubinow are outlined. Consistency with these theories is verified in the limit as the smoothing parameter vanishes. Numerical issues of the resulting theories are addressed in the context of test problems. This work has been a collaboration with Michael Nicholas of the Colorado School of Mines. |
| 10:25 AM 10:30 AM | Question and Answer |
| 10:30 AM 11:00 AM | Break |
| 11:00 AM 11:10 AM | Anna-Karin Tornberg - Morning Blitz Session Talk (10-16-2012) (Anna-Karin Tornberg) A spectrally accurate fast summation method and its application to simulation of fiber suspensions. |
| 11:00 AM 11:30 AM | Blitz Session |
| 11:10 AM 11:20 AM | Sorin Mitran - Morning Blitz Session Talk (10-16-2012) (Sorin Mitran) Sensitivity of cilia-induced transport to fluid rheology, axoneme structure, and dynein forcing |
| 11:20 AM 11:25 AM | Sarah Olson - Morning Blitz Session Talk (10-16-2012) (Sarah Olson) Modeling Hyperactivated Sperm Motility |
| 11:20 AM 11:30 AM | Karin Leiderman - Morning Blitz Session Talk (10-16-2012) (Karin Leiderman) A Simple Model of Ciliary Beating in Doubly-Periodic Stokes Flow |
| 11:25 AM 11:30 AM | Saverio Spagnolie - Morning Blitz Session Talk (10-16-2012) (Saverio Spangolie) Helices swim slower... and faster... in a viscoelastic fluid |
| 11:30 AM 12:30 PM | Panel-led Discussion |
| 11:30 AM 11:35 AM | Robert Dillon - Morning Blitz Session Talk (10-16-2012) (Robert Dillon) Models for Complex Fluid-Structure Interaction in Sperm and Ciliary Motility |
| 11:35 AM 11:40 AM | Sookkyung Lim - Morning Blitz Session Talk (10-16-2012) (Sookkyung Lim) Bundling formation of bacterial helical flagella in a viscous fluid. |
| 11:40 AM 11:45 AM | Kenny Breuer - Morning Blitz Session (10-16-2012) (Kenny Breuer) Speed of a Swimming Sheet in Newtonian and Viscoelastic Fluids |
| 12:30 PM 02:00 PM | Lunch Break |
| 02:00 PM 02:45 PM | William Davis |
| 02:45 PM 02:55 PM | Question and Answer |
| 02:55 PM 03:25 PM | Zvonimir Dogic - From molecular motors to synthetic cilia and beyond The emergence of single molecule experimental techniques coupled with the development of in vitro motility assays has revolutionized our knowledge of how isolated molecular motors convert chemical energy from ATP hydrolysis into a continuous linear movement along microtubules or actin filaments. However, biology abounds with examples ranging from periodic beating of eukaryotic cilia to macroscopic contraction of skeletal muscle wherein thousands of molecular motors coordinate their movement on molecular lengthscales to produce entirely new dynamics at macroscopic scales. Studying such emergent phenomena presents significant experimental challenges but also an opportunity to gain insight into fundamental biological processes while simultaneously uncovering fundamental physics of systems that are driven to highly out-of-equilibrium states. In this vein, our group has focused on reconstituting far-from-equilibrium structures from purified biochemical components. I will describe recent advances in this area including: (1) assembly of a minimal model of synthetic cilia capable of generating periodic beating patterns, (2) study of 2D active liquid crystals and (3) reconstitution of cytoplasmic streaming within micron sized droplets. |
| 03:25 PM 03:30 PM | Questions and Answer |
| 03:30 PM 04:00 PM | Break |
| 04:00 PM 04:10 PM | Winfield Sale - Aspects of Regulation of Motility Aspects of Regulation of Motility |
| 04:10 PM 04:20 PM | Guilherme Garcia - Fluid homeostasis and its influence on cilia motility Fluid homeostasis and its influence on cilia motility |
| 04:20 PM 04:30 PM | Chris O'Callaghan - Aspects of motility disruption as modeled by PCD Aspects of motility disruption as modeled by PCD |
| 04:30 PM 05:30 PM | Panel-led Discussion |
| 05:30 PM | Shuttle pick-up from MBI |
| 06:15 PM 06:45 PM | Cash Bar |
| 06:45 PM 06:45 PM | Banquet in the Fusion Room @ Crowne Plaza Hotel |
| Wednesday, October 17, 2012 | |
|---|---|
| Time | Session |
| 08:15 AM | Shuttle to MBI |
| 08:45 AM 09:00 AM | Breakfast |
| 09:00 AM 09:45 AM | Michael Shelley - Analytical and numerical approaches for understanding fluid-structure interactions in ciliary systems Analytical and numerical approaches for understanding fluid-structure interactions in ciliary systems |
| 09:45 AM 09:55 AM | Question and Answer |
| 09:55 AM 10:25 AM | Ramin Golestanian |
| 09:55 AM 10:25 AM | Ramin Golestanian - Hydrodynamic Synchronization, Coordination, and Signalling Microorganisms and the mechanical components of the cell motility machinery such as cilia and flagella operate in low Reynolds number conditions where hydrodynamics is dominated by viscous forces. The medium thus induces a long-ranged hydrodynamic interaction between these active objects, which could lead to synchronization, coordination and other emergent many-body behaviors. In my talk, I will examine these effects using minimal models that are simple enough to allow extensive analysis that sheds light on the underlying mechanisms for the emergent phenomena. |
| 10:25 AM 10:30 AM | Question and Answer |
| 10:30 AM 11:00 AM | Break |
| 11:00 AM 11:30 AM | Greg Forest - Flow and Diffusive Transport Properties of Mucus vs. Concentration Flow and Diffusive Transport Properties of Mucus vs. Concentration |
| 11:00 AM 11:30 AM | Blitz session (Three 10-minute talks) |
| 11:30 AM 12:30 PM | Panel-led discussion |
| 12:30 PM 02:00 PM | Lunch Break |
| 02:00 PM 02:20 PM | Anna-Karin Tornberg - A spectrally accurate fast summation method and its application to simulation of fiber suspensions In microfluidic applications, the Reynolds number is often very small, and the dynamics of the fluid can be described by the Stokes equations, which can be reformulated as a boundary integral equation. Numerical simulations based on boundary integral formulations can be accelerated using a fast summation method. I will present a spectrally accurate FFT based Ewald method for this purpose. This method allows for the use of much smaller FFT grids, as compared to established methods. The method has been adopted to the simulation of rigid fiber suspensions, and modified to allow for analytic integration for fibers that are close. Due to the relative smallness of the FFT grids, it is possible to treat larger periodic domains, including a larger number of fibers, and still fit in on a desktop. I will also discuss the extension of our spectral Ewald method to the case of planar periodicity (periodic in two of the three dimensions), a case for which no fast Ewald methods previously existed for Stokes. |
| 02:20 PM 02:40 PM | Sorin Mitran |
| 02:25 PM 02:45 PM | Sorin Mitran - Sensitivity of cilia-induced transport to fluid rheology, axoneme structure, and dynein forcing A fluid-structure interaction model that couples viscoelastic fluid motion induced by collective behavior of cilia to detailed axoneme mechanics is used to investigate bounds on cilia structure and mucus properties that determine effective fluid clearance. Dynein forcing is represented by a stochastic walker model that responds to local ATP concentrations provided by a biochemical network model. Cilium axonemes are modeled by large-deflection finite elements representing microtubules and viscoelastic springs representing connecting elements (nexins, radial spokes). Cilium motion is coupled to a viscoelastic fluid computation that models gel-like behavior of the mucus as well as possible Newtonian behavior of the periciliary fluid layer. Behavior of the viscoelastic fluid is prescribed at a microscopic level to avoid using continuum viscoelastic models of questionable validity. A lattice-based technique based upon a variational formulation of the Fokker-Planck equation is used to describe the viscoelastic fluid dynamics. A lattice Boltzmann method is applied to capture forcing of the viscoelastic mucus layer by concurrent airflow. The overall model exhibits natural formation of metachronal waves due to phase coupling of the dynein motion. Adjoint density analysis and uncertainty quantification techniques are applied to assess the stability of the transport induced by metachronal waves to perturbations in dynein walker rates, axoneme element rigidity, and mucus gel-formation process. The goal is not only to assess the robustness of the metachronal transport process, but also to identify elements within the overall transport mechanism that are most promising targets for pharmaceutical treatment of ciliary dysfunction. |
| 02:40 PM 03:00 PM | Karin Leiderman |
| 02:50 PM 03:10 PM | Karin Leiderman - A Simple Model of Ciliary Beating in Doubly-Periodic Stokes Flow In this talk, I will introduce a regularization method that gives a smooth formulation for the fundamental solution to Stokes flow driven by an infinite, triply-periodic array of point forces. With this formulation, the velocity at any spatial location may be calculated, including at and very near the point forces; these locations typically lead to numerical difficulties due to the singularity within the Stokeslet when using other methods. For computational efficiency, the current method is built upon previous methods in which the periodic Stokeslet is split into two rapidly decaying sums, one in physical space and one in reciprocal, or Fourier, space. I will show a few validation studies and then discuss a recent extension of the method to doubly-periodic flow. Finally, using the extended method, simulations of doubly-periodic arrays of beating cilia will be presented. |
| 03:00 PM 03:35 PM | Break |
| 03:35 PM 04:45 PM | Organizing committee & theme teams sequestered for report writing |
| 04:45 PM | Shuttle pick-up from MBI |
| Thursday, October 18, 2012 | |
|---|---|
| Time | Session |
| 08:15 AM | Shuttle to MBI |
| 08:45 AM 09:00 AM | Breakfast |
| 09:00 AM 09:20 AM | Sarah Olson - Modeling Hyperactivated Sperm Motility Sperm are known to exhibit two distinct types of motility. One is characterized by constant amplitude, symmetrical waveforms. The other is characterized by asymmetrical waveforms, which are correlated with an increase in calcium concentration. The goal of this work is to model the undulatory swimming of sperm swimming in a viscous, incompressible fluid using the method of regularized Stokeslets. Varying waveforms will be considered via a preferred curvature function. Results showing emergent waveforms, swimming speeds, and trajectories will be compared to experimental data. |
| 09:25 AM 09:45 AM | Saverio Spagnolie - Helical bodies swim slower... and faster... through a viscoelastic fluid Many microorganisms swim by rotating one or many helical flagella, often propelling themselves through fluids that exhibit both viscous and elastic qualities in response to deformations. In an effort to better understand the complex interaction between the fluid and body in such systems, we have studied numerically the force-free swimming of a rotating helix in a viscoelastic (Oldroyd-B) fluid. The introduction of viscoelasticity can either enhance or retard the swimming speed depending on the body geometry and the properties of the fluid (through a dimensionless Deborah number). The results are compared to recent experiments on a rotating helix immersed in a Boger fluid. Our findings bridge the gap between studies showing situationally dependent enhancement or retardation of swimming speed, and may help to clarify phenomena observed in a number of biological systems. |
| 09:50 AM 10:05 AM | Robert Dillon - Models for complex fluid-structure interaction in sperm and ciliary motility The motility of sperm flagella and cilia are based on a common axonemal structure. This structure is capable of generating a wide range of dynamical behavior modulated by signaling molecules as well as the properties of the fluid environment. We describe a fluid-mechanical model for the axoneme coupling the internal force generation of dynein molecular motors through the passive elastic axonemal structure with the external fluid mechanics. As shown in numerical simulations, the model's flagellar waveform depends strongly on viscosity as well as dynein strength. We show an extension of our original model for Newtonian fluids to complex viscoelastic fluids in order to model mucus transport by cilia in the respiratory tract as well as sperm motility in reproduction. These immersed boundary models for sperm and ciliary motility in complex fluids explore continuum approaches such as Oldroyd-B as well as Lagrangian moving mesh methods. |
| 10:10 AM 10:30 AM | Sookkyung Lim |
| 10:30 AM 11:00 AM | Break |
| 11:00 AM 12:00 PM | Preview of workshop reports & feedback |
| 12:00 PM 12:15 PM | Closing Remarks |
| 12:15 PM 12:15 PM | One shuttle back to hotel and one shuttle to Columbus Airport (CMH) |
| Name | Affiliation | |
|---|---|---|
| Ardekani, Arezoo | aardekan@nd.edu | Aerospace and Mechanical Engineering, University of Notre Dame |
| Boucher, Richard | richard_boucher@med.unc.edu | CF Center, University of North Carolina, Chapel Hill |
| Bouzarth, Elizabeth | liz.bouzarth@furman.edu | Mathematics, Furman University |
| Breuer, Kenny | kbreuer@brown.edu | School of Engineering, Brown University |
| Brueckner, Martina | martina.brueckner@yale.edu | Pediatrics and Genetics, Yale University |
| Cortez, Ricardo | rcortez@tulane.edu | Mathematics Dept., Tulane University |
| Davis, C. | cwdavis@med.unc.edu | Cystic Fibrosis/Pulmonary Research & Treatment Center, University of North Carolina, Chapel Hill |
| Dillon, Robert | dillon@math.wsu.edu | Department of Mathematics, Washington State University |
| Dogic, Zvonimir | zdogic@brandeis.edu | Physics, Brandeis University |
| Fauci, Lisa | fauci@tulane.edu | Mathematics, Tulane University |
| Feng, Yan | jennyyanfeng@gmail.com | Applied Mathematic, University of North Carolina, Chapel Hill |
| Fermigier, Marc | fermi@pmmh.espci.fr | Physics, ESPCI |
| Forest, Mark | forest@amath.unc.edu | Mathematics, Biomedical Engineering, University of North Carolina, Chapel Hill |
| Gaffney, Eamonn | eamonn.gaffney@maths.ox.ac.uk | Mathematical Institute, University of Oxford |
| Garcia, Guilherme | :guilhermejmgarcia@gmail.com | Biotechnology and Bioengineering Center, Medical College of Wisconsin |
| Ghosh, Ambarish | ambarish@ece.iisc.ernet.in | Indian Institute of Science, Bangalore |
| Golestanian, Ramin | ramin.golestanian@physics.ox.ac.uk | Physics, University of Oxford |
| Hill, Kent | kenthill@mednet.ucla.edu | MIMG, University of Southern California |
| Ho, Nguyenho | nho@wpi.edu | Mathematical Science, Worcester Polytechnic Institute |
| Hohenegger, Christel | choheneg@math.utah.edu | Mathematics, University of Utah |
| Karpman, Kara | kjk13@duke.edu | Mathematics, Duke University |
| King, Stephen | sking@nso2.uchc.edu | Molecular Microbial and Structural Biology, University of Connecticut Health Center |
| Layton, Anita | alayton@math.duke.edu | Mathematics, Duke University |
| Lechtreck, Karl | lechtrek@uga.edu | Cellular Biology, University of Georgia |
| Leiderman, Karin | kleiderman@ucmerced.edu | Applied Mathematics, University of California Merced |
| Lim, Sookkyung | sookkyung.lim@uc.edu | Mathematical Biosciences Institute (MBI), The Ohio State University |
| Makouangou Ngouma, Michael Evrard | michaelevrard@aims.ac.za | Mathematics, University of Kwazulu-natal, Westville Campus |
| Martindale, James | jmartind@live.unc.edu | Mathematics, University of North Carolina, Chapel Hill |
| McLaughlin, Rich | rmm@amath.unc.edu | mathematics, University of North Carolina, Chapel Hill |
| Mitran, Sorin | mitran@unc.edu | Mathematics, University of North Carolina, Chapel Hill |
| OCallaghan, Chris | co54@leicester.ac.uk | Paediatrics, University of Leicester |
| Olson, Sarah | sdolson@wpi.edu | Department of Mathematical Sciences, Worcester Polytechnic Institute |
| Praetorius, Helle | hp@fi.au.dk | Dept. of Biomedicine (physiology), Aarhus University |
| Salathe, Matthias | MSalathe@med.miami.edu | Medicine/Pulmonary, University of Miami |
| Sale, Winfield | wsale@emory.edu | Cell Biology, Emory University |
| Satir, Peter | peter.satir@einstein.yu.edu | Anatomy and Structural Biology, Albert Einstein College of Medicine |
| Sears, Patrick | searspr@med.unc.edu | Cystic Fibrosis, University of North Carolina, Chapel Hill |
| Shelley, Michael | shelley@cims.nyu.edu | The Courant Institute, New York University |
| Shinar, Tamar | shinar@cs.ucr.edu | Computer Science and Engineering, University of California, Riverside |
| Sircar, Sarthok | sircar1981@gmail.com | Applied Mathematics, University of Colorado |
| Spagnolie, Saverio | Saverio_Spagnolie@Brown.edu | Mathematics, University of Wisconsin |
| Superfine, Rich | rsuper@physics.unc.edu | Physics and Astronomy, University of North Carolina, Chapel Hill |
| Tornberg, Anna-Karin | annak@nada.kth.se | Numerical Analysis, KTH - Royal Institute of Technology |
| Vasquez, Paula | pvasquez@unc.edu | Mathematics, University of North Carolina, Chapel Hill |
| Xu, Ling | xulingsue@gmail.com | Mathematics and Statistics, Georgia State University |
| Zhao, Longhua | lzhao@math.umn.edu | School of Mathematics, University of Minnesota |
Afternoon Blitz Session Talk (10-15-2012) (Arezoo Ardekani)
Blitz Session (Arezoo Ardekani)
Afternoon Blitz Session Talk (10-15-2012) (Kenny Breuer)
Afternoon Blitz Session Talk (10-15-2012) (Kenny Breuer)
Morning Blitz Session (10-16-2012) (Kenny Breuer)
Speed of a Swimming Sheet in Newtonian and Viscoelastic Fluids
Cilia in the Development of Left-right asymmetry
Cilia in the Development of Left-right asymmetry
Slender body theory using regularized Stokeslets
Slender-body theories allow for the representation of thin tubes in Stokes' flow by a distribution of fundamental solutions along the filament center line while approximately enforcing boundary conditions on the surface of the tube. The idea is revisited here in the more general setting of regularized forces in a small neighborhood of the center line. The regularity in the forces produces a smooth final expression that helps eliminate the computational instabilities of the unregularized formulas. The derivations of the regular slender body theories corresponding with the standard theories of Lighthill and of Keller and Rubinow are outlined. Consistency with these theories is verified in the limit as the smoothing parameter vanishes. Numerical issues of the resulting theories are addressed in the context of test problems.
This work has been a collaboration with Michael Nicholas of the Colorado School of Mines.
This work has been a collaboration with Michael Nicholas of the Colorado School of Mines.
Models for complex fluid-structure interaction in sperm and ciliary motility
The motility of sperm flagella and cilia are based on a common axonemal structure. This structure is capable of generating a wide range of dynamical behavior modulated by signaling molecules as well as the properties of the fluid environment. We describe a fluid-mechanical model for the axoneme coupling the internal force generation of dynein molecular motors through the passive elastic axonemal structure with the external fluid mechanics. As shown in numerical simulations, the model's flagellar waveform depends strongly on viscosity as well as dynein strength. We show an extension of our original model for Newtonian fluids to complex viscoelastic fluids in order to model mucus transport by cilia in the respiratory tract as well as sperm motility in reproduction. These immersed boundary models for sperm and ciliary motility in complex fluids explore continuum approaches such as Oldroyd-B as well as Lagrangian moving mesh methods.
Morning Blitz Session Talk (10-16-2012) (Robert Dillon)
Models for Complex Fluid-Structure Interaction in Sperm and Ciliary Motility
From molecular motors to synthetic cilia and beyond
The emergence of single molecule experimental techniques coupled with the development of in vitro motility assays has revolutionized our knowledge of how isolated molecular motors convert chemical energy from ATP hydrolysis into a continuous linear movement along microtubules or actin filaments. However, biology abounds with examples ranging from periodic beating of eukaryotic cilia to macroscopic contraction of skeletal muscle wherein thousands of molecular motors coordinate their movement on molecular lengthscales to produce entirely new dynamics at macroscopic scales. Studying such emergent phenomena presents significant experimental challenges but also an opportunity to gain insight into fundamental biological processes while simultaneously uncovering fundamental physics of systems that are driven to highly out-of-equilibrium states. In this vein, our group has focused on reconstituting far-from-equilibrium structures from purified biochemical components. I will describe recent advances in this area including: (1) assembly of a minimal model of synthetic cilia capable of generating periodic beating patterns, (2) study of 2D active liquid crystals and (3) reconstitution of cytoplasmic streaming within micron sized droplets.
Computational models of ciliary dynamics: successes and challenges
The beating of a cilium is an elegant example of an actuated elastic structure coupled to a surrounding fluid. Computational fluid dynamics enthusiasts will recognize that ciliary systems present many complications such as the interaction of groups of cilia, the influence of boundaries, and the coupling to fluids that have complex rheology and microstructures. Moreover, the ciliary beatform is an emergent feature of these mechanical considerations along with biochemical processes. We will present an overview of current CFD models of cilia, along with some recent progress in analyzing fluid mixing by cilia and modeling ciliary penetration of a mucus layer.
Engineered microswimmers and micropumps
Since the pioneering studies of GI Taylor in the fifties, models have been used to gain understanding in the propulsion of microorganisms. Modern microfabrication techniques enable us to assemble very small scale devices emulating the motion of cilia. I will review the different strategies used in recent years towards the goal of fabricating micron scale artificial swimmers. In particular I will discuss the relative merits of self-assembly and micromolding. I will describle several sources of propulsive energy but most of the talk will be devoted to magnetically driven systems.
Flow and Diffusive Transport Properties of Mucus vs. Concentration
Flow and Diffusive Transport Properties of Mucus vs. Concentration
Fluid homeostasis and its influence on cilia motility
Fluid homeostasis and its influence on cilia motility
Magnetically actuated helical nanostructures
Maneuvering nanoscale objects in fluidic media in a non-invasive manner can lead to various biomedical applications, and is pursued by researchers across many disciplines. Of particular interest is the possibility of powering and controlling the motion of nanoscale objects with small, homogeneous magnetic fields, which is easy to achieve, and guaranteed to be non-invasive as well. This has recently been achieved by various groups using advanced nanofabrication techniques, where magnetic nanoscale objects of different shapes, such as helical, flexible rod-likeetc. have been maneuvered in a controllable fashion using either rotating or undulating magnetic fields. In particular, cork-screw motion is achieved in ferromagnetic helical nanostructures by aligning the permanent magnetic moments of the helix with a rotating magnetic field, causing the nanostructure to rotate and therefore propel. Such systems have been referred to as either magnetic nanopropellers or as artificial bacterial flagella in the literature. In this talk, we will discuss the fabrication and actuation of such a system, and describe their complex dynamical behavior in the presence of thermal fluctuations. In particular, we will describe how this novel system can show bistable dynamics and may have non-gaussian speed fluctuations under certain conditions.
Hydrodynamic Synchronization, Coordination, and Signalling
Microorganisms and the mechanical components of the cell motility machinery such as cilia and flagella operate in low Reynolds number conditions where hydrodynamics is dominated by viscous forces. The medium thus induces a long-ranged hydrodynamic interaction between these active objects, which could lead to synchronization, coordination and other emergent many-body behaviors. In my talk, I will examine these effects using minimal models that are simple enough to allow extensive analysis that sheds light on the underlying mechanisms for the emergent phenomena.
Afternoon Blitz Session Talk (10-15-2012) (Ramin Golestanian)
Blitz Session (Ramin Glestanian)
Planarians as a Genetically Tractable Model for a Ciliated Epithelium
The planarian ventral surface is a completely exposed ciliated epithelium. These animals utilize their motile cilia to generate gliding locomotion by beating against secreted mucus. The ventral cilia have a standard 9+2 axoneme containing both inner and outer rows of dynein arms and beat at ~22 Hz. RNAi knockdown approaches are simple and robust, leading to reductions in mRNA to almost undetectable levels. Thus, planaria may be used to rapidly screen proteins of unknown function for their role in ciliary assembly and/or motility, and may also provide a useful model system in which to investigate muco-ciliary interactions. I will discuss the use of this organism to analyze the role of outer arm dynein components in generating motile force and in maintaining the hydrodynamic coupling required for metachronal synchrony of beating cilia.
Ciliary Motility- outside and inside
The ventricular system in the brain is lined by multiciliated cells. The motility of these ependymal cilia was analyzed in hy3-/- mice which carry a null mutation in Hydin and develop lethal hydrocephalus. Hy3-/- cilia lack a projection from the ciliary central pair and move with slightly reduced beat frequency and a greatly reduced beat amplitude. They lack the ability to generate fluid flow explaining the hydrocephalic phenotype of the mutant mice. The assembly of motile and non-motile cilia requires intraflagellar transport (IFT) but it remains largely unknown how IFT traffics ciliary precursors. Simultaneous in vivo imaging of IFT and cargoes revealed a complex pattern of IFT and non-IFT cargo movements, and unloading and assembly site docking events. Quantitative data on cargo frequency, assembly, and turn-over will provide a basis for future modeling of ciliary assembly and dynamics.
A Simple Model of Ciliary Beating in Doubly-Periodic Stokes Flow
In this talk, I will introduce a regularization method that gives a smooth formulation for the fundamental solution to Stokes flow driven by an infinite, triply-periodic array of point forces. With this formulation, the velocity at any spatial location may be calculated, including at and very near the point forces; these locations typically lead to numerical difficulties due to the singularity within the Stokeslet when using other methods. For computational efficiency, the current method is built upon previous methods in which the periodic Stokeslet is split into two rapidly decaying sums, one in physical space and one in reciprocal, or Fourier, space. I will show a few validation studies and then discuss a recent extension of the method to doubly-periodic flow. Finally, using the extended method, simulations of doubly-periodic arrays of beating cilia will be presented.
Morning Blitz Session Talk (10-16-2012) (Karin Leiderman)
A Simple Model of Ciliary Beating in Doubly-Periodic Stokes Flow
Morning Blitz Session Talk (10-16-2012) (Sookkyung Lim)
Bundling formation of bacterial helical flagella in a viscous fluid.
Sensitivity of cilia-induced transport to fluid rheology, axoneme structure, and dynein forcing
A fluid-structure interaction model that couples viscoelastic fluid motion induced by collective behavior of cilia to detailed axoneme mechanics is used to investigate bounds on cilia structure and mucus properties that determine effective fluid clearance. Dynein forcing is represented by a stochastic walker model that responds to local ATP concentrations provided by a biochemical network model. Cilium axonemes are modeled by large-deflection finite elements representing microtubules and viscoelastic springs representing connecting elements (nexins, radial spokes). Cilium motion is coupled to a viscoelastic fluid computation that models gel-like behavior of the mucus as well as possible Newtonian behavior of the periciliary fluid layer. Behavior of the viscoelastic fluid is prescribed at a microscopic level to avoid using continuum viscoelastic models of questionable validity. A lattice-based technique based upon a variational formulation of the Fokker-Planck equation is used to describe the viscoelastic fluid dynamics. A lattice Boltzmann method is applied to capture forcing of the viscoelastic mucus layer by concurrent airflow. The overall model exhibits natural formation of metachronal waves due to phase coupling of the dynein motion. Adjoint density analysis and uncertainty quantification techniques are applied to assess the stability of the transport induced by metachronal waves to perturbations in dynein walker rates, axoneme element rigidity, and mucus gel-formation process. The goal is not only to assess the robustness of the metachronal transport process, but also to identify elements within the overall transport mechanism that are most promising targets for pharmaceutical treatment of ciliary dysfunction.
Morning Blitz Session Talk (10-16-2012) (Sorin Mitran)
Sensitivity of cilia-induced transport to fluid rheology, axoneme structure, and dynein forcing
Aspects of motility disruption as modeled by PCD
Aspects of motility disruption as modeled by PCD
Modeling Hyperactivated Sperm Motility
Sperm are known to exhibit two distinct types of motility. One is characterized by constant amplitude, symmetrical waveforms. The other is characterized by asymmetrical waveforms, which are correlated with an increase in calcium concentration. The goal of this work is to model the undulatory swimming of sperm swimming in a viscous, incompressible fluid using the method of regularized Stokeslets. Varying waveforms will be considered via a preferred curvature function. Results showing emergent waveforms, swimming speeds, and trajectories will be compared to experimental data.
Morning Blitz Session Talk (10-16-2012) (Sarah Olson)
Modeling Hyperactivated Sperm Motility
---and everything will flow
Primary cilia are able to sense flow. This is these years a banality � or is it? The question has been addressed with quite many approaches. And at least for a long row of mechano-sensitive cells, especially epithelial cells with long cilia this seem to hold. The primary cilium is not in itself necessary for a cell to be mechano-sensitive. If the stimulus were substantial enough any cell would react to mechanical stimulation. The cilium merely sensitise a given cell to mechanical stimuli � and that gives a challenge when one wants to address the ciliary effects. First of all they are subtle, which means that one has to titrate the system to catch these effects without mechanically over-stimulating the cells. Nevertheless, when addressing the sensory functions of cilia, mechanical or receptory � less is more. The talk is a short overview over the cilum as a flow censor and how to catch the signal.
Aspects of Regulation of Motility
Aspects of Regulation of Motility
Analytical and numerical approaches for understanding fluid-structure interactions in ciliary systems
Analytical and numerical approaches for understanding fluid-structure interactions in ciliary systems
Helical bodies swim slower... and faster... through a viscoelastic fluid
Many microorganisms swim by rotating one or many helical flagella, often propelling themselves through fluids that exhibit both viscous and elastic qualities in response to deformations. In an effort to better understand the complex interaction between the fluid and body in such systems, we have studied numerically the force-free swimming of a rotating helix in a viscoelastic (Oldroyd-B) fluid. The introduction of viscoelasticity can either enhance or retard the swimming speed depending on the body geometry and the properties of the fluid (through a dimensionless Deborah number). The results are compared to recent experiments on a rotating helix immersed in a Boger fluid. Our findings bridge the gap between studies showing situationally dependent enhancement or retardation of swimming speed, and may help to clarify phenomena observed in a number of biological systems.
Morning Blitz Session Talk (10-16-2012) (Saverio Spangolie)
Helices swim slower... and faster... in a viscoelastic fluid
Afternoon Blitz Session Talk (10-15-2012) (Rich Superfine)
Blitz Session Talk (Rich Superfine)
A spectrally accurate fast summation method and its application to simulation of fiber suspensions
In microfluidic applications, the Reynolds number is often very small, and the dynamics of the fluid can be described by the Stokes equations, which can be reformulated as a boundary integral equation.
Numerical simulations based on boundary integral formulations can be accelerated using a fast summation method. I will present a spectrally accurate FFT based Ewald method for this purpose. This method allows for the use of much smaller FFT grids, as compared to established methods. The method has been adopted to the simulation of rigid fiber suspensions, and modified to allow for analytic integration for fibers that are close. Due to the relative smallness of the FFT grids, it is possible to treat larger periodic domains, including a larger number of fibers, and still fit in on a desktop. I will also discuss the extension of our spectral Ewald method to the case of planar periodicity (periodic in two of the three dimensions), a case for which no fast Ewald methods previously existed for Stokes.
Numerical simulations based on boundary integral formulations can be accelerated using a fast summation method. I will present a spectrally accurate FFT based Ewald method for this purpose. This method allows for the use of much smaller FFT grids, as compared to established methods. The method has been adopted to the simulation of rigid fiber suspensions, and modified to allow for analytic integration for fibers that are close. Due to the relative smallness of the FFT grids, it is possible to treat larger periodic domains, including a larger number of fibers, and still fit in on a desktop. I will also discuss the extension of our spectral Ewald method to the case of planar periodicity (periodic in two of the three dimensions), a case for which no fast Ewald methods previously existed for Stokes.
Morning Blitz Session Talk (10-16-2012) (Anna-Karin Tornberg)
A spectrally accurate fast summation method and its application to simulation of fiber suspensions.
Afternoon Blitz Session Talk (10-15-2012) (Arezoo Ardekani) Arezoo Ardekani Blitz Session (Arezoo Ardekani)
Afternoon Blitz Session Talk (10-15-2012) (Rich Superfine) Rich Superfine Blitz Session Talk (Rich Superfine)
Helical bodies swim slower... and faster... through a viscoelastic fluid Saverio Spagnolie Many microorganisms swim by rotating one or many helical flagella, often propelling themselves through fluids that exhibit both viscous and elastic qualities in response to deformations. In an effort to better understand the complex interaction betwe
Modeling Hyperactivated Sperm Motility Sarah Olson Sperm are known to exhibit two distinct types of motility. One is characterized by constant amplitude, symmetrical waveforms. The other is characterized by asymmetrical waveforms, which are correlated with an increase in calcium concentration. The go
Hydrodynamic Synchronization, Coordination, and Signalling Ramin Golestanian Microorganisms and the mechanical components of the cell motility machinery such as cilia and flagella operate in low Reynolds number conditions where hydrodynamics is dominated by viscous forces. The medium thus induces a long-ranged hydrodynamic in
Sensitivity of cilia-induced transport to fluid rheology, axoneme structure, and dynein forcing Sorin Mitran A fluid-structure interaction model that couples viscoelastic fluid motion induced by collective behavior of cilia to detailed axoneme mechanics is used to investigate bounds on cilia structure and mucus properties that determine effective fluid clea
Computational models of ciliary dynamics: successes and challenges Lisa Fauci The beating of a cilium is an elegant example of an actuated elastic structure coupled to a surrounding fluid. Computational fluid dynamics enthusiasts will recognize that ciliary systems present many complications such as the interaction of groups o
Engineered microswimmers and micropumps Marc Fermigier Since the pioneering studies of GI Taylor in the fifties, models have been used to gain understanding in the propulsion of microorganisms. Modern microfabrication techniques enable us to assemble very small scale devices emulating the motion of cilia
Ciliary Motility- outside and inside Karl Lechtreck The ventricular system in the brain is lined by multiciliated cells. The motility of these ependymal cilia was analyzed in hy3-/- mice which carry a null mutation in Hydin and develop lethal hydrocephalus. Hy3-/- cilia lack a projection from the cili
Cilia in the Development of Left-right asymmetry Martina Brueckner Cilia in the Development of Left-right asymmetry