RESEARCH NEWS & VIEWS sensitivities for one of the detectors at the Laser Inter­ferometer Gravitational-Wave Observatory in Richland, Washington3. The starting point for Lo and colleagues’ study is a single calcium ion (Ca+) trapped by radio­frequency electromagnetic fields in a vacuum vessel. One can picture the trapped ion as a tiny pendulum oscillating around its equilibrium position. For a quantum pendulum in its lowest energy state, the uncertainties in its position and momentum have equal magnitude. In this case, squeezing corresponds to suppressing position fluctuations at the cost of momentum, or vice versa. The authors use a set of methods known as laser cooling to bring the ion to its motional ground state4, and then introduce additional laser fields to squeeze the state, reducing the positional variance by a factor of nine. Although squeezed states of trapped ions were first demonstrated 19 years ago5, the fidelity with which these delicate states are prepared is highly sensitive to experimental noise, such as fluctuating electric and magnetic fields. The authors used a technique called reservoir engineering, which was previously developed by the same research group6, to achieve robust, high-fidelity squeezing even in the presence of noise. With the ion in a squeezed ground state, the next step is to prepare it in a cat-state super­ position. Imagine that the ion pendulum is displaced by pulling it to one side, then releasing it; it will swing back and forth with the amplitude that has been imparted. Now imagine pulling the ion to the right and left at the same time: classically this does not make sense, but quantum mechanically it is possible. The way to do this with a trapped ion is to apply a state-dependent force — a displacement whose direction depends on the spin state of the ion’s outermost electron1. When the electron is prepared in a superposition of two spin states, the force acts in an equal and opposite direction on each component. As a result, the ion pendulum’s motion is a superposition of two possible oscillations, each with the same amplitude but in opposite directions. In fact, each motional direction is entangled with the electron’s spin state; that is, one property cannot be described independently of the other. How distinguishable are the two cat-state components from each other? It depends on whether the initial squeezing was performed on the ion’s position or on its momentum. Lo and colleagues measured and compared the two cases. If momentum fluctuations were suppressed before the cat state was prepared, then the corresponding enhancement in position fluctuations made the spatial separation more difficult to distinguish. By contrast, if the ion’s position was squeezed, then the spatial separation between the components became 56 times larger than the extent of the squeezed positional fluctuations.

It is exactly this amplified sensitivity to spatial separation that makes squeezed states promising for future applications. For example, using cat states, the wave nature of a single ion can be exploited for interferometry. In an interferometer, a wave is split, sent along two paths and finally recombined, providing information about how the paths differ. In a cat state, the ion’s location is split into two superposition components, each of which explores a different path. Thus, if the cat-state components are recombined, the superposition acts as an interferometer, probing path differences. Moreover, an ion is highly sensitive to changes in electric and magnetic fields, which shift its electron energy levels, so an ion interferometer could measure field gradients on the scale of tens of nanometres7. Squeezed cat states would also be more robust than non-squeezed states to certain types of noise, providing improved sensing capabilities. Building on established techniques for the precise manipulation of trapped ions, the authors have demonstrated an exciting new capability for both engineering and characterizing quantum states. These states are fascinating, not only as future sensors, but also as a means of exploring the boundary between the quantum and classical worlds. The ion

pendulum demonstrated by Lo and colleagues has a position uncertainty of only a few nanometres, but it swings back and forth — in two directions at once — over hundreds of nanometres, a much larger distance than atomic scales. Efforts are under way in many research groups to extend cat-state length scales even further, into truly macroscopic regimes. Future work with squeezed cat states will continue to characterize their strange, often counter-intuitive, quantum properties. Here, as the authors have shown, single ions provide an exceptional experimental platform on which to do so. ■ Tracy Northup is at the Institut für Experimentalphysik, Universität Innsbruck, Innsbruck 6020, Austria. e-mail: [email protected] 1. Monroe, C., Meekhof, D. M., King, B. E. & Wineland, D. J. Science 272, 1131–1136 (1996). 2. Lo, H.-Y. et al. Nature 521, 336–339 (2015). 3. Aasi, J. et al. Nature Photon. 7, 613–619 (2013). 4. Leibfried, D., Blatt, R., Monroe, C. & Wineland, D. Rev. Mod. Phys. 75, 281–324 (2003). 5. Meekhof, D. M., Monroe, C., King, B. E., Itano, W. M. & Wineland, D. J. Phys. Rev. Lett. 76, 1796–1799 (1996). 6. Kienzler, D. et al. Science 347, 53–56 (2015). 7. Poyatos, J. F., Cirac, J. I., Blatt, R. & Zoller, P. Phys. Rev. A 54, 1532–1540 (1996).

STEM C EL L S

Asymmetric rejuvenation Organelles called mitochondria are asymmetrically apportioned to the daughters of dividing stem cells according to mitochondrial age. This finding sheds light on the mechanisms underlying asymmetric stem-cell division. ANU SUOMALAINEN

T

he thought of reversing the ageing process has tickled the human imagination for centuries. Despite the air of mystery surrounding the topic, rejuvenation occurs so naturally that we pay no attention to it — that is, when mothers give birth to offspring. Although babies originate from the germ cells of a mother and father who might be decades old, they do not inherit their parents’ accumulated cellular damage, but get a fresh start. Writing in Science, Katajisto et al.1 suggest that such rejuvenation may also be a characteristic of the stem cells responsible for tissue maintenance. Stem cells have some distinctive characteristics. They are long-lived, or even immortal, and can divide asymmetrically2. The differ­ ence between the daughter cells of an asymmetric stem-cell division is not subtle. One

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daughter inherits the mother’s immortality and ability to give rise to many cell types. The other must leave the cosy stem-cell home, become mortal and commit to differentia­ ting into a cell with a specialized identity, for example a cell of the gut wall, eschewing its broad potential in favour of excelling at one particular task. Katajisto et al.1 focused on the stem cells of human mammary tissue. Samples taken from the tissue and cultured in vitro contain small, round, stem-cell-like cells and flat epithelial cells, which line the mammary ducts in vivo. The different daughters of mammary stem-cell divisions are therefore easily distinguished by microscopy, and their fates can be followed in vitro. To investigate whether asymmetric stem-cell division involves asymmetric apportioning of organelles to the two daughters, the authors developed assays that enabled them to tag organelles and then activate the tags at

NEWS & VIEWS RESEARCH

Nucleus

Dividing stem cell

Newly synthesized mitochondria

Old mitochondria

Stem-cell-like daughter

Tissue-progenitor daughter

Figure 1 | Unequal sharing between daughters.  Tissue stem cells undergo asymmetric cell division, in which one daughter cell adopts a stem-cell-like state and the other differentiates into a more-specialized cell type. Katajisto et al.1 report that organelles called mitochondria are split unevenly between the two daughters. Older organelles, which are located in the region surrounding the nucleus of the mother cell, are apportioned primarily to the tissue-progenitor daughter, whereas newly synthesized mitochondria are apportioned to the stem-cell-like daughter.

exact times. In this way, they could identify the organelles that were newly synthesized and those that were old, and track them after cell division. The researchers observed that the various types of organelle were similarly distributed between the two daughters, with one exception. Organelles called mitochondria showed differential segregation, such that the multi-talented stem-cell daughter received most of the newly synthesized mitochondria, whereas the tissueprogenitor daughter received around six times more old mitochondria (Fig. 1). Thus, organellar rejuvenation occurs in tissue stem cells, and involves mitochondria. Mitochondria use oxygen to burn fats, sugars and amino acids, generating ATP molecules that act as the cell’s energy currency. This oxidative metabolism establishes an electric charge (a membrane potential) across the membrane surrounding the organelle3 that can be used as a measure of mitochondrial ATP synthesis. Oxidative metabolism also generates side products in the form of reactive oxygen species (ROS) — potent signalling molecules that, if produced in excess, can damage surrounding proteins, lipids and DNA. Subtle changes in ROS can modify stem-cell behaviour, promoting commitment to differentiation4. Indeed, mitochondrial dysfunction promotes stem-cell dysfunction and exhaustion, leading to premature signs of ageing that mimic physiological ageing5–7. By contrast, fully functional mitochondrial proteins minimize ROS production and maximize control

over oxidative metabolism. It is therefore no surprise that stem cells treasure prime fitness in this organelle. The concept of apportioning old mito­ chon­dria asymmetrically has already been established in baker’s yeast, in which damaged proteins and mitochondria with lower oxidative function preferentially remain in the mother cell 8,9, rather than entering the daughter that buds off from it. By contrast, Katajisto et al. found no functional differences between the mitochondria apportioned to the different daughter cells, because the membrane potential was similar in both types of cell. Even when the authors abolished the membrane potential, asymmetric apportioning occurred. In fact, the only determinant of mitochondrial fate was organellar age. Katajisto and colleagues showed that ageing mitochondria were preferentially located close to the nucleus, whereas young organelles were also found in the cell periphery (Fig. 1). This suggests that physical segregation of the organelles contributes to differential delivery during cell division. Chemical inhibition of the fission process by which mitochondria divide hindered this compartmentalization, indicating a key role for mitochondrial dynamics in asymmetric mitochondrial segregation. Asymmetric mitochondrial apportioning could be an indication of the general selfishness of stem cells — the cells that end up being mortal are largely unimportant compared with their immortal sisters. This hypothesis would

be consistent with the ‘disposable soma’ theory of ageing10 (extended here to apply to tissue stem cells), which posits that an organism is merely disposable packing material for its germ cells. The second possibility, however, is that the committed daughter cell actually requires old mitochondria to fulfil its function. Mitochondrial ATP synthesis increases on differentiation, and an increase in ROS in response to increased mitochondrial function is associated with differentiation4. For example, in red blood cells, subtle increases in ROS orchestrate iron loading and cell maturation11. The asymmetric apportioning of mitochondria could therefore provide the ROS boost required to initiate a differentiation program. The ultimate fate of old mitochondria during the differentiation of tissue-progenitor daughters remains an open question. Eventually they will be recycled, and new organelles will replace them. The authors noticed that asymmetric apportioning of mitochondria required the presence of parkin, a protein that marks mitochondria for recycling12. However, there were no apparent changes in recycling levels in daughter cells. Whether parkin has a role, for example, in the timing of degradation of the old organelles after division remains unknown. Katajisto and colleagues’ study raises questions about the role of mitochondrial quality control as a regulator of cell fate and behaviour. For instance, an exciting possibility is that the mechanism described is a general feature of stem cells. It will be interesting to investigate whether similar mechanisms are in place in mature tissues. Furthermore, it is unclear how stem cells would handle increased mitochondrial-protein damage in mitochondrial disorders. Another avenue for study is what happens to mitochondrial DNA during asymmetric mitochondrial apportioning. And finally, do similar mechanisms apply in germ cells, providing the offspring with a fresh mitochondrial start? Defining the molecular mechanisms underlying this phenomenon will bring us a step closer to understanding the cellular recipe for immortality — the rejuvenation of energy metabolism. ■ Anu Suomalainen is in the Research Programs Unit, Molecular Neurology, Biomedicum-Helsinki, University of Helsinki, Helsinki 00290, Finland. e-mail: [email protected] 1. Katajisto, P. et al. Science 348, 340–343 (2015). 2. Mukherjee, S., Kong, J. & Brat, D. J. Stem Cells Dev. 24, 405–416 (2015). 3. Nunnari, J. & Suomalainen, A. Cell 148, 1145–1159 (2012). 4. Ito, K. & Suda, T. Nature Rev. Mol. Cell Biol. 15, 243–256 (2014). 5. Ahlqvist, K. J. et al. Cell Metab. 15, 100–109 (2012). 6. Trifunovic, A. et al. Nature 429, 417–423 (2004). 2 1 M AY 2 0 1 5 | VO L 5 2 1 | NAT U R E | 2 9 7

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RESEARCH NEWS & VIEWS 7. Kujoth, G. C. et al. Science 309, 481–484 (2005). 8. Aguilaniu, H., Gustafsson, L., Rigoulet, M. & Nyström, T. Science 299, 1751–1753 (2003).

9. McFaline-Figueroa, J. R. et al. Aging Cell 10, 885–895 (2011). 10. Kirkwood, T. B. L. Nature 270, 301–304 (1977).

MAT E R IALS SCIENCE

Magnetic alloys break the rules A family of alloys has been discovered that undergoes unexpected changes of shape when magnetized. This strange behaviour might help in unravelling the mystery of a phenomenon called magnetic hysteresis. See Letter p.340 RICHARD D. JAMES

O

ne of the biggest puzzles in materials science is magnetic hysteresis — an effect in which the magnetization of a material depends on present and past applied magnetic fields. Hard magnets, which resist demagnetization in magnetic fields, have exceptionally large hysteresis (Fig. 1a). By contrast, soft magnets become fully magnetized under a small applied magnetic field, spontaneously demagnetize when the field is removed and have the smallest known hysteresis (Fig. 1b). But so little is known about hysteresis that rule-of-thumb strategies for developing alloys intended to increase the hardness of magnets sometimes lead to softer ones. The report by Chopra and Wuttig1 (page 340) of a new kind of magnetic alloy that has near-zero hysteresis presents fresh opportunities to study the mechanism of this perplexing phenomenon. The need to understand magnetic hysteresis is becoming increasingly urgent2,3. That is

because hard magnets are main components of the motors of electric vehicles and technologies such as wind-power generators, both of which are becoming more widespread. Soft magnets are ubiquitous in the electronic devices that control power in electric motors and current flow in electrical grids. So why is hysteresis so hard to comprehend? It depends intimately on the behaviour of magnetic domains in a material4,5, which can be exceedingly complex, as Chopra and Wuttig describe. But despite the geometric complexity, domain configuration is ultimately determined by a few fundamental material constants and by the shape of the magnetic body. Magnetic domains may also interact with the boundaries of the small crystals (grains) from which the material is composed, and with defects — non-magnetic impurities that inevitably form in alloys — in ways that affect hysteresis. How the fundamental constants conspire with these structural aspects to deliver a specific hysteresis profile is little understood. But hysteresis profiles (loops)

b Soft

a Hard

c Autarkic M

M

M 011

111 100

H

H

H100 or H011 or H111

Figure 1 | Typical hysteresis loops in hard, soft and autarkic magnets.  Hysteresis loops define the average magnetization, M, of a material in the direction of an applied alternating magnetic field, H, as the field is increased and then decreased. a, Hard magnets are difficult to magnetize and demagnetize, and have the largest hysteresis loops. Arrows indicate whether H was increasing or decreasing as each part of the loop was measured. b, Soft magnets become fully magnetized in a small magnetic field and exhibit small hysteresis. c, Chopra and Wuttig1 report alloys with ‘autarkic’ magnetic domains that undergo large, direction-dependent shape changes in magnetic fields, and which require a fairly large field to be magnetized, but have near-zero hysteresis and the same magnetization curves in all directions of a crystal. The indices 011, 111 and 100 denote different directions in the crystal lattice of the material in which the magnetic field is applied. 2 9 8 | NAT U R E | VO L 5 2 1 | 2 1 M AY 2 0 1 5

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11. Ahlqvist, K. J. et al. Nature Commun. 6, 6494 (2015). 12. Narendra, D., Tanaka, A., Suen, D.-F. & Youle, R. J. J. Cell Biol. 183, 795–803 (2008).

are quite reproducible in alloys that have the same composition and that are processed in similar ways. One of the constants mentioned above, K1, quantifies the difficulty of rotating the direction of magnetization within a crystal. Most researchers regard it as the most important fundamental property affecting hysteresis: a high K1 is associated with large hysteresis, and a low K1 with small hysteresis. The constants λ100 and λ111 are also thought to be relevant. These quantify magnetostriction (changes in shape of materials owing to magnetization) in two crystallographic directions, defined as 100 and 111; high values indicate large shape changes. But the precise role of these fundamental constants is not clear. For example, two of the softest magnetic materials are permalloys6: one is 55% iron and 45% nickel; the other contains 21.5% iron and 78.5% nickel. The K1 for the first permalloy is quite large, which suggests that the alloy should have a large hysteresis. But its hysteresis is actually small, so K1 alone does not tell the whole story. Moreover, K1 becomes zero for an iron–nickel mixture that has 75% nickel, which suggests that this alloy should be particularly soft — but it is not. By contrast, the (softest) 78.5% nickel permalloy has a fairly small, non-zero K1, which suggests that it should be harder than the 75% nickel alloy, but it is not. Intriguingly, the magnetostriction constants also become zero at nickel compositions close to 78.5%, but not at precisely that composition: λ100 is zero at 83% , whereas λ111 is zero at 80%. The only other composition of iron– nickel alloys at which λ100 is zero is precisely that of the first permalloy (45% nickel), which suggests that magnetostriction is relevant to softness. The discrepancies between the values of the constants and the resulting magnetic behaviour constitute the long-standing ‘perm­alloy problem’7. Although there are vague comments in the literature about the possible involvement of stress in determining hysteresis in these materials, its precise role is unclear. We certainly do not have a theory that predicts the composition of the softest permalloy to be 78.5% nickel. To unravel this mystery, it is crucial to find magnetic materials that exhibit new behaviours. Chopra and Wuttig have discovered a family of alloys that behave in three unusual ways. First, the alloys are decidedly ‘nonJoulian’: most magnetic materials retain their overall volume during magnetostriction, whereas the authors’ alloys expand considerably. A major implication of this is that the model used almost universally to quantify

Stem cells: Asymmetric rejuvenation.

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