David Voss

The 110% Solution

In a Nota Bene item, Voss discusses results recently reported in Physical Review Letters in which lasers were used to initiate crystallization of a supersaturated solution. Earlier such observations were the results of photochemical changes, but the latest findings indicate a purely nonchemical, photophysical alignment and clustering of molecules as the trigger.

One Plus One Is Not Two

typical class II molecule includes only small amounts of CLIP. Most of the peptides are a sampling of the proteins present within the endocytic pathway of APCs. How is this CLIP-to-antigenic-peptide switch accomplished? Evidence that other proteins were necessary for antigenic peptide loading came in 1992: Class II molecules from certain mutant APCs contain only CLIP in the binding groove and not the normal diverse array of antigenic peptides (3). The basis for this defect turned out to be the absence of a functional DM protein in these cells (4). These results indicated that DM either prevented CLIP binding to class II molecules, prevented CLIP generation, or removed CLIP from class II molecules. Late in 1995, three groups independently found that DM could remove CLIP from class II molecules and that this removal greatly enhanced antigenic peptide binding to class II molecules (5). What was puzzling, however, was that DM was able to facilitate the dissociation ofCLIP from class II but did not have the same action on other, nonCLIP peptides from class II molecules. Despite the remarkable similarity between the structure of class Il-CLIP and class Il-antigenic peptide complexes, DM could tell the difference. It appeared as though DM was seeing something that we could not, perhaps the subtle differences between the two types of class II-peptide complexes. The new paper ofWeber et al. (1) exploits their observation that the ability of DM to facilitate CLIP removal depends on the presence of certain CLIP amino acid residues that associate with pockets in the class II peptide binding groove. When one of these residues of CLIP is replaced with a corresponding residue of a non-CLIP peptide, DM can no longer catalyze the dissociation of the modified CLIP peptide from class II. By measuring the ability of DM to catalyze the removal of the mutated CLIPs from class II molecules, the authors found that the ability of a given class Il-CLIP complex to dissociate in the presence ofDM is directly proportional to the intrinsic rate of dissociation of that peptide from class II. They determined that if a given peptide analog dissociates from class II very slowly, it is not a good substrate for DM-induced dissociation, whereas those peptides that dissociate from class II rapidly (like wild-type CLIP) are very good substrates for DM. So how does DM catalyze peptide dissociation from class II molecules? Weber et al. propose that DM functions by stabilizing a transition state of the class II-peptide complex in which hydrogen bonds between the class II molecule and bound peptide are transiently disrupted. The majority of the hydrogen bonds between class II molecules and antigenic peptides (or CLIP) are between class II and the peptide main-chain atoms. (Perhaps this is why CLIP associates with essentially all class II alleles.) Because all peptides are thought to bind to class II molecules similarly, the class II-peptide mainchain bond energy is also similar. It is this phenomenon that allows DM to exert its effects in a manner that is directly proportional to the intrinsic rate of dissociation of a given peptide: Because the class II-peptide bond energy is lowered by DM by a constant amount, peptides that have additional stabilizing forces are resistant to the effects ofDM, whereas those that do not have such forces readily dissociate. One can imagine a model of DM function in which DM binds to the class II molecule to transiently pry open the peptide-binding groove by a certain amount. The net effect of this is to disrupt the normal hydrogen bonds between the class II molecule and the bound peptide, so that only those peptides with additional stabilizing forces remain associated with the class II molecule. For example, ifa particular peptide has very strong anchor residues, this transient disruption by DM will not destabilize the peptide enough to lead to its dissociation. This model also predicts that there are few additional stabilizing forces in the class IICLIP complex, and so the complex readily dissociates in the presence of DM. The exact physical mechanism by which DM exerts this effect remains unknown, although DM seems to bind directly to class II molecules (6), a finding that supports the proposed model. Regardless of the mechanism, however, it is clear that in the cell DM prevents peptides with fast intrinsic dissociation rates from remaining bound to class II molecules, independent of the overall affinity of the peptide for class II. Antigenic peptides that have fast dissociation rates are removed by DM in vivo so that they do not appear in the normal array of peptides eluted from class II molecules. In this sense, DM is acting as a true peptide editor, ensuring that only stable peptides remain bound to class II.

PHYSICS: Exciting the Nucleus

PHYSICS Modern laser sources can generate sufficient intensity to induce nuclear reactions. However, the excitation mechanism is indirect: optical laser photons deliver energy to electrons, creating a plasma, and the electrons in turn heat the nuclei sufficiently to overcome the barrier to fission

Biologically Inspired Networking

COMPUTER SCIENCE Biological systems are typically better at adapting to new situations than computers because their design emphasizes robustness and sustainability even though the proximal response may not be the optimal one. In an information network such as the Internet, data are broken up into packets before being transmitted, and each packet can take a different path across the nodes of the network. How might a method for data transmission over multiple paths be redesigned whereby the network can itself adapt to an unpredictable and fluctuating environment? Leibnitz et al. based their biologically inspired network routing scheme on a model developed to account for the response of Escherichia coli bacteria to variations in nutrient availability. The model uses stable attractors: equilibrium states into which the system settles until disrupted by a change in the environment, at which point the system converges to a new attractor. For network switching, information about the data paths (available bandwidth or transit time) is collected to find a stable attractor. When conditions change (for example, if a link breaks), a new attractor is selected, and the packets are switched to a new path. Because randomness is an intrinsic feature of the optimization method, the system is highly stable in noisy environments. — DV Commun. Assoc. Comput. Mach. 49 , 63 (2006).

ASTROPHYSICS: Signs of Collapse

ASTROPHYSICS When their nuclear fuel is exhausted, stars die, and the residual iron core collapses on itself. The outcome of a stars death throes depends on mass, however. Stars with between 10 and 20 times the mass of the Sun collapse in a spectacular explosion known as a supernova, leaving behind

The String Revolution Will Be Televised

The Elegant Universe. NOVA. WGBH Science Unit, Boston. On PBS, Tuesday evenings, 28 October (parts 1 and 2) and 4 November (part 3). www.pbs.org/wgbh/nova/elegant/ In a three-hour miniseries full of dazzling graphics, the PBS series NOVA and Brian Greene present the claims and strangeness of string theory.

Atomic Squeeze Play Stops Light Cold

In papers in Physical Review Letters and Nature , scientists report that they have used atomic gases to grab light pulses, squeeze them into a smaller space, imprint them on atoms, and read them out again after a delay. The researchers speculate that such sleight-of-light tricks might one day be useful in the still theoretical field of quantum information processing.

Nuclei Crash Through The Looking-Glass

HIGH-ENERGY PHYSICSFor the first time, physicists have discovered that atomic nuclei come in right- and left-handed models. In the 5 February issue of Physical Review Letters , a team of researchers reports observations of rapidly spinning nuclei morphing into mirror-image forms. In the process, the physicists also uncovered solid evidence that a long-disputed feature of nuclear anatomy really does exist.

Nota Bene: Unmasking Melodious Sounds

The Physics of Musical Instruments 2nd ed. Neville H. Fletcher and Thomas D. Rossing. Springer, New York, 1998. 776 pp.

Approaching the quantum gate

69.95. ISBN 0-387-98374-0. Fletcher and Rossing revise and update their comprehensive quantitative analysis of music-making devices and provide an entirely new chapter on the materials science of instruments.