CTW: Mathematical and Computational Challenges in Cilia- and Flagella-Induced Fluid Dynamics

(October 15,2012 - October 18,2012 )

Organizers


Kenny Breuer
School of Engineering, Brown University
Mark Forest
Mathematics, Biomedical Engineering, University of North Carolina, Chapel Hill
Anita Layton
Mathematics, Duke University
Matthias Salathe
Medicine/Pulmonary, University of Miami
Peter Satir
Anatomy and Structural Biology, Albert Einstein College of Medicine

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
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
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 - 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.
11:00 AM
11:30 AM

Blitz Session

11:10 AM
11:20 AM
Sorin Mitran
11:20 AM
11:25 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.
11:20 AM
11:30 AM
Karin Leiderman
11:25 AM
11:30 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.
11:30 AM
12:30 PM

Panel-led Discussion

11:30 AM
11:35 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.
11:35 AM
11:40 AM
Sookkyung Lim
11:40 AM
11:45 AM
Kenny Breuer - Afternoon Blitz Session Talk (10-15-2012) (Kenny Breuer)
Afternoon Blitz Session Talk (10-15-2012) (Kenny Breuer)
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
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
02:40 PM
03:00 PM
Karin Leiderman
02:50 PM
03:10 PM
Karin Leiderman
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
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.
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.
Morning Blitz Session Talk (10-16-2012) (Anna-Karin Tornberg)
A spectrally accurate fast summation method and its application to simulation of fiber suspensions.
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Afternoon Blitz Session Talk (10-15-2012) (Arezoo Ardekani)
Arezoo Ardekani Blitz Session (Arezoo Ardekani)

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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

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Cilia in the Development of Left-right asymmetry
Martina Brueckner Cilia in the Development of Left-right asymmetry

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Afternoon Blitz Session Talk (10-15-2012) (Rich Superfine)
Rich Superfine Blitz Session Talk (Rich Superfine)

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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

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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

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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

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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

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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

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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