Tissues and organisms

Propulsion of African trypanosomes is driven by bihelical waves with alternating chirality separated by kinks
Jose A. Rodrígueza, Miguel A. Lopez, Michelle C. Thayer, Yunzhe Zhao, Michael Oberholzer, Donald D. Chang, Neville K. Kisalu, Manuel L. Penichet, Gustavo Helguera, Robijn Bruinsma, Kent L. Hill, and Jianwei Miao
Trypanosoma brucei, a parasitic protist with a single flagellum, is the causative agent of African sleeping sickness. Propulsion of T. brucei was long believed to be by a drill-like, helical motion. Using millisecond differential interference-contrast microscopy and analyzing image sequences of cultured procyclic-form and bloodstream-form parasites, as well as bloodstream-form cells in infected mouse blood, we find that, instead, motility of T. brucei is by the propagation of kinks, separating left-handed and right-handed helical waves. Kink-driven motility, previously encountered in prokaryotes, permits T. brucei a helical propagation mechanism while avoiding the large viscous drag associated with a net rotation of the broad end of its tapering body. Our study demonstrates that millisecond differential interference-contrast microscopy can be a useful tool for uncovering important short-time features of microorganism locomotion.
PDFs: zpq19322.pdf (15.10 MB)
PNGs: Propulsion of African trypanosomes is drivenby bihelical waves with alternating chiralityseparated by kinks.png (903.81 KB)
Research categories: Tissues and Organisms, Nonequilibrium physics


Photocontrol of Protein Activity in Cultured Cells and Zebrafish with One- and Two-Photon Illumination
Deepak Kumar Sinha, Pierre Neveu, Nathalie Gagey, Isabelle Aujard, Chouaha Benbrahim-Bouzidi, Thomas Le Saux, Christine Rampon, Carole Gauron, Bernard Goetz, Sylvie Dubruille, Marc Baaden, Michel Volovitch, David Bensimon, Sophie Vriz and Ludovic Jullien
We have implemented a noninvasive optical method for the fast control of protein activity in a live zebrafish embryo. It relies on releasing a protein fused to a modified estrogen receptor ligand binding domain from its complex with cytoplasmic chaperones, upon the local photoactivation of a nonendogenous caged inducer. Molecular dynamics simulations were used to design cyclofen-OH, a photochemically stable inducer of the receptor specific for 4-hydroxy-tamoxifen (ERT2). Cyclofen-OH was easily synthesized in two steps with good yields. At submicromolar concentrations, it activates proteins fused to the ERT2 receptor. This was shown in cultured cells and in zebrafish embryos through emission properties and subcellular localization of properly engineered fluorescent proteins. Cyclofen-OH was successfully caged with various photolabile protecting groups. One particular caged compound was efficient in photoinducing the nuclear translocation of fluorescent proteins either globally (with 365 nm UV illumination) or locally (with a focused UV laser or with two-photon illumination at 750 nm). The present method for photocontrol of protein activity could be used more generally to investigate important physiological processes (e.g., in embryogenesis, organ regeneration and carcinogenesis) with high spatiotemporal resolution.
JPEGs: Photocontrol of Protein Activity in Cultured Cells.jpg (348.34 KB)
PDFs: Photocontrol of Protein Activity in Cultured Cells.pdf (6.06 MB)
Research categories: Tissues and Organisms, Experimental probes


One-dimensional deterministic transport in neurons measured by dispersion-relation phase spectroscopy
Ru Wang , Zhuo Wang, Joe Leigh, Nahil Sobh, Larry Millet, Martha U Gillette, Alex J Levine and Gabriel Popescu
Professor Levine, working with experimental colleagues at the University of Illinois at Urbana-Champaign, explores the “traffic jams” in transport of vesicles down the narrow neural filaments, axons and and dendrites.
JPEGs: One-dimensional deterministic transport.jpg (1.04 MB)
PDFs: One-dimensional-deterministic-transport.pdf (7.20 MB)


Frequency-dependent Chemotactic Target Selection
Sarah A. Nowak, Buddhapriya Chakrabarti, Tom Chou, and Ajay Gopinathan, Frequency-dependent Chemotactic Target Selection, Physic
Chemotaxis is often modeled in the context of cellular motion towards a static, exogenous source of chemoattractant. Here, we propose a time-dependent mechanism of chemotaxis in which a motile particle (the cell) releases a chemical that diffuses to fixed particles (targets) and signals the production of a second chemical by these targets. The motile cell moves up concentration gradients of this second chemical. When one target is present, we describe probe release strategies that optimize travel of the cell to the target. In the presence of multiple targets, the one selected by the cell depends on the strength and, interestingly, on the frequency of probe chemical release. Although involving an additional chemical signaling step, our chemical ``pinging'' hypothesis allows for greater flexibility in regulating target selection, as seen in a number of physical or biological realizations.
PDFs: 1478-3975_7_2_026003.pdf (3.01 MB)
PNGs: Chemotactic signals emanating from two communicating organisms.png (907.28 KB)
Research categories: Tissues and Organisms, Nonequilibrium physics, Experimental probes


A mathematical model for intercellular signaling during epithelial wound healing
Posta and Chou, A mathematical model for intercellular signaling during epithelial wound healing, Journal of Theoretical Biology
Filippo Posta, Tom Chou
Recent experiments monitoring the healing process of wounded epithelial monolayers have demonstrated the necessity of MAPK activation for coordinated cell movement after damage. This MAPK activity is characterized by two wave-like phenomena. One MAPK ``wave'' that originates immediately after injury, propagates deep into the cell sheet, away from the edge, and then rebounds back to the wound interface. After this initial MAPK activity has largely disappeared, a second MAPK front propagates slowly from the wound interface and also continues into the cell sheet, maintaining a sustained level of MAPK activity throughout the cell sheet. It has been suggested that the first wave is initiated by Reactive Oxygen Species (ROS) generated at the time of injury. Here, we develop a minimal mathematical model that reproduces the observed behavior. The main ingredients of our model are a competition between ligands and ROS for the activation of Epithelial Growth Factor Receptor, and a feedback loop between receptor occupancy and MAPK activation. We explore the mathematical properties of the model and look for traveling wave solutions consistent with the experimentally observed MAPK activity patterns.
PDFs: jtb_final.pdf (3.55 MB)
PNGs: A mathematical model for intercellular signaling during epithelial wound healing.png (2.71 MB)
Research categories: Tissues and Organisms, Nonequilibrium physics


Bacteria Use Type IV Pili to Walk Upright and Detach from Surfaces
M. L. Gibiansky, J. C. Conrad, F. Jin, V. D. Gordon, D. A. Motto, M. A. Mathewson, W. G. Stopka, D. C. Zelasko, J. Shrout, G. C. L. Wong, “Bacteria use type IV pili to stand, walk upright, and detach from surfaces”, Science, 330, 197 (2010).
Maxsim L. Gibiansky, Jacinta C. Conrad, Fan Jin, Vernita D. Gordon, Dominick A. Motto, Margie A. Mathewson, Wiktor G. Stopka, Daria C. Zelasko, Joshua D. Shrout, Gerard C. L. Wong
Bacterial biofilms are structured multicellular communities involved in a broad range of infections. Knowing how free-swimming bacteria adapt their motility mechanisms near surfaces is crucial for understanding the
transition between planktonic and biofilm phenotypes. By translating microscopy movies into searchable databases of bacterial behavior, we identified fundamental type IV pili–driven mechanisms for Pseudomonas aeruginosa surface motility involved in distinct foraging strategies. Bacteria stood upright and “walked” with trajectories optimized for two-dimensional surface exploration. Vertical orientation facilitated surface detachment and could influence biofilm morphology.
JPEGs: Gerard Wong group discovers walking bacteria.jpg (397.02 KB)
PDFs: Science Gibiansky Conrad Wong 2010.pdf (21.73 MB)
Research categories: Cellular mechanics, Tissues and Organisms, Nonequilibrium physics


Depiction of a localized retinal delamination
Chou and Siegel, The mechanics of retinal detachment, Submitted to: Physical Biology, (2012).
Chou, Siegel
We present a model of the mechanical and fluid forces associated with retinal detachments where the retinal photoreceptor cells separate from the underlying retinal pigment epithelium (RPE). We determine the conditions under which the subretinal fluid pressure exceeds the maximum yield stress holding the retina and RPE together, giving rise to an irreversible, extended retinal delamination. For detachments induced by traction forces, we find a critical radius beyond which the blister is unstable to growth. Growth of a detached blister can also be driven by inflamed tissue within which, for example, the hydraulic conductivities of the retina or choroid increase, the RPE pumps fail, or the adhesion properties change. We determine the parameter regimes in which the blister either becomes unstable to growth, remains stable and finite-sized, or shrinks, allowing possible healing. The corresponding stable blister radius and shape are calculated. Our analysis provides a quantitative description of the physical mechanisms involved in exudative retinal detachments and can help guide the development of retinal reattachment protocols or preventative procedures.
PNGs: Depiction of a localized retinal delamination.png (153.42 KB)


Bacteria use type IV pili to slingshot on surfaces
F. Jin, J. C. Conrad, M. L. Gibiansky, G. C. L. Wong, “Bacteria use type IV pili to slingshot on surfaces”, Proc. Nat. Acad. Sci. USA, 108 12617-12622 (2011).
Fan Jina, Jacinta C. Conrad, Maxsim L. Gibianskya, and Gerard C. L. Wong
Bacteria optimize the use of their motility appendages to move efficiently on a wide range of surfaces prior to forming multicellu- lar bacterial biofilms. The “twitching” motility mode employed by many bacterial species for surface exploration uses type-IV pili (TFP) as linear actuators to enable directional crawling. In addition to linear motion, however, motility requires turns and changes of direction. Moreover, the motility mechanism must be adaptable to the continually changing surface conditions encountered during biofilm formation. Here, we develop a novel two-point tracking algorithm to dissect twitching motility in this context. We show that TFP-mediated crawling in Pseudomonas aeruginosa consistently alternates between two distinct actions: a translation of constant velocity and a combined translation-rotation that is approximately 20× faster in instantaneous velocity. Orientational distributions of these actions suggest that the former is due to pulling by multiple TFP, whereas the latter is due to release by single TFP. The release action leads to a fast “slingshot” motion that can turn the cell body efficiently by oversteering. Furthermore, the large velocity of the slingshot motion enables bacteria to move efficiently through environments that contain shear-thinning vis- coelastic fluids, such as the extracellular polymeric substances (EPS) that bacteria secrete on surfaces during biofilm formation.
JPEGs: Wong group discovers ‘slingshoting’ bacteria.jpg (363.20 KB)
PDFs: PNAS Jin Wong 2011.pdf (7.95 MB)


The physics of retinal detachments
Tom Chou, Michael Siegel
We develop mathematical model describing the mechanical and fluid forces associated with ex- udative retinal detachments. We assume that the retina adheres to the underlying retinal pigment epitelium (RPE) cells layer via an attractive interaction potential that can be irreversibly destroyed. By computing the total water flow arising from transretinal, vascular, and retinal pigment epithe- lium (RPE) pump currents, we determine the conditions under which the subretinal fluid pressure exceeds the maximum yield stress holding the retina and RPE together, giving rise to an extended retinal delamination. We also investigate localized, blister-like retinal detachments by balancing mechanical tension in the retina with both the chorioretinal adhesion energy and the pressure jump across the retina. For detachments formed by traction, we find a critical radius beyond which the blister is unstable to unbounded growth. On the other hand, if growth of the detached blister is further driven by inflamed choroidal tissue (in which e.g., the RPE pumps do not function), we find in certain cases the blister size depends simply on two parameters, the normal-tissue, dimensionless RPE pump flux, and a dimensionless combination comprising the retinal stretching elasticity, the retina-RPE adhesion energy, and the area of the inflamed lesion. We find parameter regimes which lead to either a finite or infinite blister radii, and to the corresponding blister shape. Our model provides a mathematical description of the physical mechanisms involved in exudative retinal de- tachments and macular edema and can guide further development of retinal reattachment protocols or preventative procedures.
JPEGs: csr-oct.jpg (3.01 MB)
Research categories: Cellular mechanics, Tissues and Organisms, Nonequilibrium physics, Soft and fragile matter