Bundling with X-rays

Bundling with X-rays

w.sciencemag.org SCIENCE VOL 327 29 JANUARY 2010529 indicating that platelets have infl ammatory functions and a substantial arsenal of factors that confer the ability to signal to monocytes, dendritic cells, and other immune effector cells. There is also evidence that platelet microparticles activate adaptive immune cells in specifi c tissue compartments in response to cues that trigger antibody synthesis and alter lymphocyte activities ( 1).

A perplexing issue is that Boilard et al. did not detect intact platelets in the synovial fluid of patients with rheumatoid arthritis, although other investigators have found them ( 7, 8). How, then, did the incendiary microparticles gain access to the joint space? One possibility is that microparticles associate with transmigrating leukocytes and are then carried into the synovial fl uid, a mechanism supported by microscopic and fl ow cytometric observations of Boilard et al.

This could happen in synovial blood vessels, where the numbers of microparticles may be much higher than reported in peripheral blood ( 9). It could also occur in extravascular synovial tissue if release of microparticles occurs as a result of platelet interactions with collagen and/or fibroblast-like synoviocytes in this compartment ( 1). Platelets adhere to activated polymorphonuclear leukocytes and monocytes in the circulation in many infl ammatory conditions ( 12), including rheumatoid arthritis ( 13). Thus, leukocytes may deliver platelets and/or microparticles to extravascular sites by this, or other, mechanisms ( 14). Polymorphonuclear leukocytes may well be accomplices that deliver microparticles to the rheumatoid arthritis joint space and, conceivably, facilitate their local formation in transit through the synovium.

References and Notes 1. E. Boilard et al., Science 327, 580 (2010). 2. S. Perez-Pujol et al., Cytometry A 71, 38 (2007). 3. M. M. Denis et al., Cell 122, 379 (2005). 4. A. E. Rosenberg, in Robbins and Cotran Pathologic Basis of

Disease, V. Kumar, A. K. Abbas, N. Favsto, J. C. Aster, Eds. (Saunders, Philadelphia, ed. 8, 2010), p. 1205–1256. 5. E. H. Choy, G. S. Panayi, N. Engl. J. Med. 344, 907 (2001). 6. F. Diaz-Gonzalez, M. H. Ginsberg, in Kelly’s Textbook of

Rheumatology, E. D. Harris Jr. et al., Eds. (Elsevier Saunders, Philadelphia, 2005), vol. 1, p. 252–259. 7. C. M. Herd, C. P. Page, in Immunopharmacology of Platelets, M. Joseph, Ed. (Academic Press, London, 1995). 8. M. Yaron, M. Djaldetti, Arthritis Rheum. 21, 607 (1978). 9. E. A. J. Knijff-Dutmer et al., Arthritis Rheum. 46, 1498 (2002). 10. G. A. Zimmerman, A. S. Weyrich, Arterioscler. Thromb.

Vasc. Biol. 28, s17 (2008). 1. D. L. Sprague et al., Blood 11, 5028 (2008). 12. A. S. Weyrich, G. A. Zimmerman, Trends Immunol. 25, 489 (2004). 13. J. E. Joseph et al., Br. J. Haematol. 115, 451 (2001). 14. T. Weissmuller et al., J. Clin. Invest. 118, 3682 (2008). 15. We thank D. Lim for assistance with the fi gure.


Bundling with X-rays MATERIALS SCIENCE

Cyrus R. Safi nya 1 and Youli Li 2

High-brilliance synchrotron radiation is used to trigger a reversible transition from randomly oriented fi laments to hexagonal bundles.


ore than a century after its discovery, x-ray irradiation continues to profoundly impact a wide range of fi elds, from screening at airports to wholebody imaging diagnostics in health care ( 1). In the natural sciences, x-ray crystallography has clarifi ed how the shapes of proteins and related complexes relate to their cellular function, and x-ray scattering has elucidated the structure and dynamics, mechanical properties, and intermolecular interactions of countless materials ( 2– 5). On page 5 of this issue, Cui et al. ( 6) report a new twist in the application of x-ray scattering, where synchrotron x-ray irradiation, in addition to its usual role in probing structure, acts as a reversible switch for self-assembly from a disordered to an ordered state of bundled fi laments (see the fi gure).

Bundling of fi lamentous proteins is widely observed in the eukaryotic cell cytoskeleton ( 7). In cells, bundles are assembled and disassembled to enable a wide range of functions. For example, filamentous actin can assemble with associating proteins into stress fi bers ending in focal adhesion spots associated with cell adhesion, or form dynamically active bundles within membrane-protruding fi lopodia in cell crawling. Another example is microtubule bundles, which are important in the development and extension of axons in neurons ( 8). The bundles are stabilized by microtubule-associated proteins and possibly other factors, which noncovalently cross-link neighboring microtubules.

Oosawa was the fi rst theorist to develop a model explaining how nanofibers carrying the same charge may form bundles ( 9).

The model, which applies generally to both biological and nonbiological fi bers, is counterintuitive, because similarly charged fi bers normally repel each other due to electrostatic forces. Oosawa showed how fl uctuations in the bound counterions of neighboring fi laments become correlated and produce an attractive force (similar to an effective van der Waals attraction), which leads to bundles. More recent theories also show the possibility of bundle formation through salt-bridge–

Barbara, CA 93106, USAMaterials Research Laboratory,

A BARBARAMaterials, Physics, and Molecular, Cellular, and Developmental Biology Departments, University of California, Santa University of California, Santa Barbara, CA 93106, USA. E- mail: safi nya@mrl.ucsb.edu; youli@mrl.ucsb

X-ray off

X-ray on

X-ray irradiation switch. In Cui et al.’s experiment, transmission of a high-brilliance synchrotron beam through the sample charges up peptide-based nanorods. As a result, the randomly oriented fi laments transition to two-dimensional ionic crystals of hexagonal bundles. The fi lament bundles revert to the disordered state after the beam is turned off.

Published by AAAS on January 29, 2010 w.sciencemag.org Downloaded from

29 JANUARY 2010 VOL 327 SCIENCE w.sciencemag.org 530 like, exponentially decaying attractive forces between neighboring fi laments ( 9).

Most experimental data on nonspecific bundling interactions appear to be consistent with theoretical predictions of densely packed bundles resulting from counterion-induced attractive forces, but substantial discrepancies remain. Microtubules can form various bundling architectures, from tight hexagonal bundles to loose two-dimensional necklacelike morphologies with linear, branched, and loop morphologies ( 10) that are not predicted by theory.

In contrast to the filament bundling described so far, which typically arises from attractive forces, long-range electrostatic repulsion appears to play the dominant role in inducing the formation of widely spaced, stable hexagonal fi lament bundles reported by Cui et al. The authors hypothesize that x-ray irradiation induces a reversible chemical reaction, with deprotonation of carboxyl groups on glutamic acid residues leading to highly charged fi laments (see the fi gure). Their observation that the induced ordered phase occurs only above a certain x-ray dose rate rather than accumulated dose is consis- tent with a reversible switching process (see the figure). The large equilibrium spacing observed by the authors seems to result from repulsive fi laments in a confi ned geometry, reminiscent of a two-dimensional Wigner crystal [where minimization of potential energy at low concentration leads to a twodimensional crystal ( 3)].

Radiation-induced structural changes are usually detrimental. The term “radiation damage” is widely used to describe the resulting structural degradation. What is unusual and interesting in Cui et al.’s study is that x-ray irradiation induces rather than destroys ordering. The system seems to be highly susceptible to hexagonal order due to the built-in electrostatic repulsive force; above a critical concentration, bundles form spontaneously without x-ray radiation. By increasing the charge of the fi laments, irradiation tips the transition point to much lower concentrations, where spontaneous bundling does not occur.

Further studies are needed to clarify the detailed x-ray–induced ionization process responsible for the ordering observed by Cui et al. Nevertheless, the x-ray switch introduced by this study opens up entirely new directions in nanoscale assembly. We expect that future work will extend the discovery to other systems, such as other peptidebased geometric shapes, including sheets and spheres. Other new directions may involve using grazing-incidence x-ray irradiation for the controlled growth of ultrathin ordered phases at interfaces.

References 1. S. G. Benka, G. B. Lubkin, Phys. Today 48, 23 (1995). 2. J. Als-Neilsen, G. Materlik, Phys. Today 48, 34 (1995). 3. P. M. Chaikin, T. C. Lubensky, Principles of Condensed

Matter Physics (Cambridge Univ. Press, Cambridge, 1995). 4. P. G. De Gennes, J. Prost, The Physics of Liquid Crystals

(Oxford Univ. Press, Oxford, ed. 2, 1993). 5. C. R. Safi nya, in The New Physics for the Twenty First

Century, G. Fraser, Ed. (Cambridge Univ. Press, Cambridge, 2006). 6. H. Cui et al., Science 327, 5 (2010); published online 17 December 2009 (10.1126/science.1182340). 7. D. Bray, Cell Movements: From Molecules to Motility

(Garland, New York, ed. 2, 2001). 8. E. R. Kandel et al., Principles of Neural Science (McGraw

Hill, New York, Singapore, ed. 4, 2000). 9. W. M. Gelbart, R. F. Bruinsma, P. A. Pincus, V. A. Parsegian, Phys. Today 53, 38 (2000). 10. D. J. Needleman et al., Proc. Natl. Acad. Sci. U.S.A. 101, 16099 (2004).


A Test for Geoengineering? ATMOSPHERIC SCIENCE

Alan Robock, 1 Martin Bunzl, 2 Ben Kravitz, 1 Georgiy L. Stenchikov 3

Stratospheric geoengineering cannot be tested in the atmosphere without full-scale implementation.

cientific and political interest in the possibility of geoengineering the climate is rising ( 1). There are currently no means of implementing geoengineering, but if a viable technology is produced in the next decade, how could it be tested? We argue that geoengineering cannot be tested without full-scale implementation. The initial production of aerosol droplets can be tested on a small scale, but how they will grow in size (which determines the injection rate needed to produce a particular cooling) can only be tested by injection into an existing aerosol cloud, which cannot be confi ned to one location. Furthermore, weather and climate variability preclude observation of the climate response without a large, decade-long forcing. Such full-scale implementation could disrupt food production on a large scale.

We use the term “geoengineering” to refer to solar radiation management (SRM), particularly the injection of aerosols into the stratosphere to emulate volcanic emissions. We consider the best case for conducting experiments in the atmosphere, putting aside some of the worst-case reservations that have been raised about the atmospheric risks of geoengineering ( 2, 3).

If ongoing climate modeling and limited experiments to test insertion methodology were to indicate that SRM would reverse many negative aspects of global warming, could these results be validated with in situ experiments to test the creation of a stratospheric aerosol cloud and the resulting climate response? Some authors have argued that the effects of polar testing could be confined to the Arctic ( 4). However, we have shown ( 5), on the basis of analogs from past volcanic eruptions and climate model experiments, that Arctic injection would cool the atmosphere down to latitude 30°N, weakening the summer monsoon over Africa and Asia and reducing precipitation, just like tropical injections of stratospheric aerosols. Indeed, any high-latitude sulfate aerosol production would affect large parts of the planet.

Even if insertion does indeed have to end up as planetwide, it might be thought that one could at least proceed at low rates of insertion and look for any untoward side effects before increasing the dose. But two major issues prevent useful testing of stratospheric aerosol injection with small amounts.

First, to produce an aerosol cloud of sufficient thickness that lasts long enough to detectably cool Earth’s surface, regular injections would be needed into air that already contains an aerosol cloud. One can fl y aircraft or balloons into the stratosphere and test nozzles and injection of material into the wake of the planes (see the fi gure) ( 6), and thereby measure the creation of aerosols in the fi rst minutes or hours into a pristine stratosphere. However, current theory tells us that continued emission of sulfur gases or sulfate particles would cause existing particles to grow to larger sizes, larger than volcanic eruptions typ-Department of Environmental Sciences, Rutgers Univer-

Saudi ArabiaE-mail: robock@envsci.rutgers.edu

sity, 14 College Farm Road, New Brunswick, NJ 08901, USA. Department of Philosophy, Rutgers University, 191 Ryders Lane, New Brunswick, NJ 08901, USA. Division of Physical Sciences and Engineering, 4700 King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Published by AAAS on January 29, 2010 w.sciencemag.org Downloaded from