seem to have moved across continents withfrightening speed, implying that there wouldbe little time to contain the spread of newresistance genes.

How can this information help us to con-trol malaria? First, although it is tempting tothink that we now know the full extent of P. falciparum diversity, further surveys arestill needed. A present-day snapshot of variation in many genes among more iso-lates, spanning broad geographical areas,will be important in determining the geneticimpact of a vaccination or expanded drugprogramme. Had thorough genetic moni-toring been in place, we might have detectedthe genetic variants causing the spread ofchloroquine resistance early enough to takesteps to prolong the usefulness of the drug.Second, we need a systematic collection ofPlasmodium isolates to be shared among

laboratories, common resources for identi-fying and confirming sequence variations ona large scale, and a common database ofinformation. We should then rapidly reachconsensus on the genetic variability andancestral demographic history of this devas-tating parasite. ■

Andrew G. Clark is in the Department of MolecularBiology and Genetics, Cornell University, Ithaca,New York 14853, USA.e-mail: andyclark@cornell.edu

1. Gandon, S., Mackinnon, M. J., Nee, S. & Read, A. F. Nature

414, 751–756 (2001).

2. Mu, J. et al. Nature 418, 323–326 (2002).

3. Wootton, J. C. et al. Nature 418, 320–323 (2002).

4. Rich, S. M., Licht, M. C., Hudson, R. R. & Ayala, F. J. Proc. Natl

Acad. Sci. USA 95, 4425–4430 (1998).

5. Volkman, S. K. et al. Science 293, 482–484 (2001).

6. Hughes, A. L. & Verra, F. Proc. R. Soc. Lond. B 268, 1855–1860

(2001).

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8. Kim, Y. & Stephan, W. Genetics 160, 765–777 (2002).

also quantify the features of the dislocationscreated and predict how the crystalmicrostructure will change with furtherindentation. Their model captures many keyfeatures observed in experiments.

A concept emphasized in their model isthe stability parameter. This is an extremelyuseful tool for analysing materials simula-tions, as it identifies the location within thematerial at which defect nucleation is occur-ring and the characteristics of the defectbeing created. For example, indentation of ametal commonly results in the creation of adislocation. Li and colleagues’ parameter notonly indicates at which atom the dislocationwill originate, but also has information onthe Burgers vector of the dislocation and thecrystallographic plane on which slip occurs.Alternatively, a brittle material undergoingtensile loading may ultimately fail because ofthe creation of a ‘microcrack’. Presumably,their parameter would again indicate theatom at which the flaw is spawned as well asproviding quantitative information, such asthe orientation of the cleavage plane.

These situations are straightforward, butthere are some materials that exhibit bothbrittle and ductile behaviour, the latteroccurring through deformation by the creation and propagation of dislocations.The transition between ductile and brittlebehaviour is an important area of researchthat has received much attention in recent years. Li et al.’s new parameter will allow a thorough investigation, through simulation,of the conditions that lead to one response or the other.

A typical case is shown in Fig. 1, where the mechanical loading at the tip of somepre-existing crack in a crystal can result ineither the atomic planes splitting apart or the

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NATURE | VOL 418 | 18 JULY 2002 | www.nature.com/nature 285

Achild tries to dish out ice cream using ametal spoon, but the neck of the spoonbends back permanently with the effort

applied. A construction worker attempts todrive a nail into a plank, only to hit it slightlyoff-centre and end up with a useless bit ofmetal that must be extracted from the wood.These examples show that ‘plasticity’, theirreversible deformation of a material,affects people’s lives on a daily basis. But howplastic deformation occurs at the atomicscale is not fully understood. A new model,presented by Li et al.1 on page 307 of thisissue, takes us further into the details of thiscomplicated process.

The term ‘plasticity’ is most commonlyused for metals and other materials that havean underlying crystal structure, where theconstituent atoms are arranged into a latticewith a repeatable pattern. When a line defect,or dislocation, is created in the structure, itmoves through the material, resulting in apermanent change in its shape2. This movement is called ‘slip’, as it refers to theslipping of adjacent atomic planes past oneanother. There has been much fundamentalresearch into what triggers, or nucleates, adislocation and how plasticity develops incrystals. As the characteristic dimension ofdislocations — the Burgers vector — is of theorder of the spacing between atoms, thesedislocations are studied using nanoscaleexperimental techniques and modelling atthe level of individual atoms — atomisticsimulation.

However, it is difficult to link the mecha-nisms at work in simulations to the obser-vations made in larger-scale physical experiments. Li et al.1 impressively combineaspects of atomistic simulation with finite-element analysis treating the crystal as a con-tinuum, to predict the onset of dislocationduring nanoindentation — when the crystalis indented to nanometre-scale depths. They

Materials science

Plastic parameterJonathan A. Zimmerman

Materials may deform permanently under pressure, but it’s difficult toguess exactly what will happen to their structure at the atomic level. A newmodel, and a powerful parameter, might allow firm predictions to be made.

Figure 1 Cracking up. When force is applied to a sharp, atom-wide crack in a material, brittle orductile behaviour may ensue. If the response is brittle behaviour (upper right), the atomic planescleave as the crack propagates. With a ductile response (lower right), the tip of the crack becomesblunted as dislocations spread through the crystal structure. Predicting whether a material willrespond in a brittle or a ductile fashion to an applied load is complicated; many factors are involved.But Li et al.1 have devised a ‘stability parameter’ that effectively models the formation andpropagation of dislocations through a material.

© 2002 Nature Publishing Group

emission and propagation of dislocations,depending on how the load is applied. Analytical3,4, computational5,6 and experi-mental7,8 studies have been carried out in an attempt to pin down the relationshipsbetween applied thermo-mechanical load-ing and the way in which a material will react. A combination of factors are usuallyinvolved: temperature8; motion or dynamicsof existing defects6,7; the specific elementsand alloys that make up the crystal5; the ori-entation of the crystal lattice with respect tothe load; the rate at which the load is applied;existing microstructural barriers such ascrystal-grain boundaries; and properties ofthe material that determine its resistance toductile and brittle deformation.

This last factor was well summarized byRice3, who compared the energetic ‘cost’ ofcreating new surfaces within the crystal (thesurface energy) with the energy barrier that must be overcome to allow atomicplanes to slip over one another (the unstablestacking fault energy). Rice used fracturemechanics to perform a straightforwardanalysis, and found that a critical ratio ofthese energies separates ductile from brittlebehaviour for a particular crystal-lattice typeand orientation.

Given the above list of factors, it is clearly difficult to predict whether a materialwill fail in a ductile or a brittle fashion. Materials scientists try to determine thecompeting mechanisms involved and toidentify properties in the material that influence nucleation and propagation. Pre-vailing theories of failure mechanics usequantities that are related to the load-bear-ing ability of a material, such as yield andfracture stresses, whereas newer methodsrely on evaluating the energetic barriersdescribed above. Complex systems willrequire a combination of these criteria toadequately describe any irreversible defor-mation process. Although it has yet to beused for this, the model devised by Li et al.1

has the potential to predict whether brittle orductile behaviour will occur.

It is in the area of predictive modellingthat the work of Li et al. will be immenselyuseful. The authors present a methodologyfor using their stability parameter in finite-element calculations — a simulation tech-nique that models materials as a continuum,but uses the same interatomic potentials as inatomistic simulations. This enables systemswith larger-than-atomic dimensions to besimulated, and can take into accountmicrostructural features such as grainboundaries and different phases of the mate-rial. There is also the exciting possibility ofrefining the approach to operate effectivelyat finite temperatures and high loading rates.Li et al. have achieved a significant steptowards understanding the defective worldof materials in which we live. ■

Jonathan A. Zimmerman is at Sandia National

Laboratories, PO Box 969, Livermore, California94551-0969, USA. e-mail: jzimmer@sandia.gov1. Li, J., Van Vliet, K. J., Zhu, T., Yip, S. & Suresh, S. Nature 418,

307–310 (2002). 2. Askeland, D. R. The Science and Engineering of Materials (PWS-

Kent, Boston, Massachusetts, 1994).

3. Rice, J. R. J. Mech. Phys. Solids 40, 239–271 (1992).4. Beltz, G. E., Lipkin, D. M. & Fischer, L. L. Phys. Rev. Lett. 82,

4468–4471 (1999).5. Farkas, D. MRS Bull. 25, 35–38 (2000).6. Abraham, F. F. J. Mech. Phys. Solids 49, 2095–2111 (2001).7. Wall, O. Eng. Fract. Mech. 69, 835–849 (2002).8. Smida, T. & Bosansky, J. Mater. Sci. Eng. A 323, 21–26

(2002).

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Within our cells are many membrane-bounded compartments, each ofwhich communicates with only a

subset of other such ‘organelles’ — generallywhen small vesicles bud off from one andmerge with another. The efficiency withwhich cells use their organelles to carry outcomplex tasks has led to the belief that move-ment through the system of organellesoccurs in strictly defined directions. So, theendoplasmic reticulum (ER) — in whichproteins destined for export from the cell aresynthesized and modified — communicatesprimarily with the Golgi apparatus. This inturn interacts with a limited set of otherorganelles and, eventually, with the plasmamembrane, defining an avenue of vesiculartraffic for protein export. In the reversedirection, extracellular molecules internal-ized by endocytosis first enter endosomesand later reach lysosomes, where they aredegraded (Fig. 1).

Although lateral communication be-tween the organelles for export and import iswell documented, their vectorial organiza-tion has been supported by the positions ofER and lysosomes at the ends of the twoavenues. But faith in these traditional routes,already shaken by studies of phagosome biogenesis1, is tested again by a report fromGagnon and colleagues2 in Cell, which showsthat proteins characteristic of the ER are present in phagosomes. This has impli-cations for our understanding of cellularorganization and of how microbes manipu-late that organization.

Phagosomes are membrane-boundedorganelles formed when one cell engulfsanother, or some inanimate particle, byenclosing it in surface membrane. Earlystudies indicated that new phagosomes weremade of plasma membrane3, and that thesubsequent merger of phagosomes withlysosomes created a phagolysosome — atoxic environment for ingested microbes. Bycurrent thinking, phagolysosomes form byprogressive interactions of phagosomes withendosomes and lysosomes4. Delivery tophagolysosomes is considered the end of the

road and a fate for ingested microbes toavoid, if possible.

So pathogens that live within host cellsenter by mechanisms that often resemblephagocytosis, but then take different routes.An early challenge to the conventional viewof organelle interactions came from studiesof Trypanosoma cruzi, which enters host cellsby stimulating the fusion of lysosomesdirectly with the plasma membrane1. Otherpathogens, such as Legionella pneumophilaand Brucella abortus, are ingested by phago-cytosis, inhibit the fusion of phagosomeswith lysosomes, and then inhabit an ER-likecompartment5.

And perhaps such seemingly extraordi-nary routes are not as uncommon as onemight think. Gagnon et al.2 have now foundthe ER acting out of order, fusing with theplasma membrane and apparently providingmembrane for phagocytosis. Using a pro-teomics approach the authors first showedthat phagosomes containing latex beads —purified from extracts of professionalphagocytic cells known as macrophages —displayed several ER marker proteins. Elec-tron microscopy then showed ER mem-branes in continuity with the plasma mem-brane near cell-bound particles. Moreover,early phagosomes contained patches of bothER and lysosomal membranes. Gagnon et al.also found that newly formed phagosomeswere enriched with ER proteins, and, asphagosomes aged inside macrophages, thelevels of ER markers diminished and thenumber of lysosomal markers increased.Strangely, the levels of ER markers in phago-somes increased again later, indicating thatphagosomes continued to fuse with ERmembranes long after phagocytosis.

Although further evidence will be neededbefore we can say that the ER is essential tophagocytosis, it is reasonable to concludethat the ER supplies membrane to somephagosomes. Phagocytosis has been shownto involve fusion of intracellular organelleswith the plasma membrane6; endosomeshave been considered the most likelyorganelles, but lysosomes and the ER can

Cell biology

The extraordinary phagosomeJoel A. Swanson

The finding that a cellular compartment called the endoplasmic reticulumcan merge with the cell’s outer membrane is surprising. It would not havebeen predicted from our knowledge of cell organization.

© 2002 Nature Publishing Group