Physics of Complex Systems

Rehovot, Israel

Physics of Complex Systems

Rehovot, Israel

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Grinvald E.,Physics of Complex Systems | Neeman L.,Physics of Complex Systems | Bar-Elli O.,Physics of Complex Systems | Ben-Zvi R.,Materials and Interfaces | And 4 more authors.
Nano Letters | Year: 2015

Facile molecular self-assembly affords a new family of organic nanocrystals that, unintuitively, exhibit a significant nonlinear optical response (second harmonic generation, SHG) despite the relatively small molecular dipole moment of the constituent molecules. The nanocrystals are self-assembled in aqueous media from simple monosubstituted perylenediimide (PDI) molecular building blocks. Control over the crystal dimensions can be achieved via modification of the assembly conditions. The combination of a simple fabrication process with the ability to generate soluble SHG nanocrystals with tunable sizes may open new avenues in the area of organic SHG materials. © 2015 American Chemical Society.


News Article | February 16, 2017
Site: phys.org

Bright-field images of a zebrafish embryo at sequential stages from the beginning to the end of doming 90 minutes later. Credit: IST The little striped zebrafish starts out as single big cell sitting on top of the yolk. During the next 3 days, cells divide and tissues move to give the fish its final shape. But how do tissues coordinate their often-complicated movements? The physical basis of tissue coordination in early zebrafish development is subject of a study by Carl-Philipp Heisenberg, Professor at the Institute of Science and Technology Austria (IST Austria) and his group, including first author and postdoc Hitoshi Morita, and colleagues at The Francis Crick Institute in London and the Max-Planck-Institute for the Physics of Complex Systems in Dresden. Until now, little has been known about how tissues coordinate their movement both temporally and spatially during development. In the study, published today in Developmental Cell, Heisenberg and co-authors investigated how tissues coordinate their movements and how the forces required for tissue movements are generated. In the paper, they show that cells at the surface are crucial for coordination. Carl-Philipp Heisenberg explains: "A reduction of surface tension by cells on the surface of the embryo is the key process that coordinates tissue movements at this timepoint." Tissue spreading is a key process both in development and disease, for example in wound healing. For a tissue, especially a complex tissue with several layers, to spread, it needs to simultaneously thin and expand. One example of such spreading is the so-called doming in the zebrafish embryo. During doming, the blastoderm, a tissue composed of surface epithelial cells and inner mesenchymal cells, thins and spreads over the yolk cell. Doming involves two tissue movements: the epithelial cell layer at the surface expands, and inner cells undergo intercalations thereby thinning and spreading the inner cell mass. In the present study, Heisenberg and his colleague asked how the two tissue movements - surface cell expansion and inner cell intercalation - coordinate their movements during blastoderm spreading. Combining theory and experiments, they show that surface cells, by undergoing active expansion, reduce the surface tension of the blastoderm. Strikingly, this loosening at the blastoderm surface not only triggers surface cell layer expansion, but also induces inner cell intercalation leading to inner cell layer thinning and spreading. Thus, the reduction in blastoderm surface tension represents the key process coordinating surface cell layer expansion with inner cell layer thinning and spreading during doming. First author Hitoshi Morita explains the significance of this study for understanding tissue spreading: "We have unravelled the force-generating processes that drive doming. Our study shows that by reducing its surface tension, the layer of epithelial cells simultaneously drives expansion and thinning of the blastoderm, and so coordinates these two processes. Coordinated tissue spreading is a universal mechanism by which embryos take shape. Understanding the force-generating mechanism is central for understanding the physical basis of embryo development. We have uncovered the key role surface cells play in this process." Explore further: Healing powers: Team detects mechanism in cell division relevant for closing wounds


News Article | February 20, 2017
Site: www.eurekalert.org

EPFL scientists have created a new computer model that can help better design of allosteric drugs, which control proteins "at a distance". Enzymes are large proteins that are involved in virtually every biological process, facilitating a multitude of biochemical reactions in our cells. Because of this, one of the biggest efforts in drug design today aims to control enzymes without interfering with their so-called active sites -- the part of the enzyme where the biochemical reaction takes place. This "at a distance" approach is called "allosteric regulation", and predicting allosteric pathways for enzymes and other proteins has gathered considerable interest. Scientists from EPFL, with colleagues in the US and Brazil, have now developed a new mathematical tool that allows more efficient allosteric predictions. The work is published in PNAS. Allosteric regulation is a fundamental molecular mechanism that modulates numerous cell processes, fine-tuning them and making them more efficient. Most proteins contain parts in their structure away from their active site that can be targeted to influence their behavior "from a distance". When an allosteric modulator molecule -- whether natural or synthetic -- binds such a site, it changes the 3D structure of the protein, thereby affecting its function. The main reason allosteric sites are of such interest to drug design is that they can be used to inhibit or improve the activity of a protein, eg. the binding strength of an enzyme or a receptor. For example, diazepam (Valium) acts on an allosteric site of the GABAA receptor in the brain, and increases its binding ability. Its antidote, flumazenil (Lanexat), acts on the same site, but instead inhibits the receptor. Generally speaking, an allosteric drug would also be used at a comparatively lower dose than a drug acting directly on the protein's active site, thus providing more effective treatments with fewer side effects. Despite the importance of allosteric processes, we still do not fully understand how a molecule binding on a distant and seemingly unimportant part of a large protein can change its function so dramatically. The key lies in the overall architecture of the protein, which determines what kinds of 3D changes an allosteric effect will have. The lab of Matthieu Wyart at EPFL sought to address several questions regarding our current understanding of allosteric architectures. Scientists classify these into two types: hinges, which cause scissor-like 3D changes, and shear, which involve two planes moving side-by-side. Despite being clear mechanically, the two models do not capture all cases of allosteric effects, where certain proteins cannot be classified as having either hinge or shear architectures. The researchers explored alternative allosteric architectures. Specifically, they looked at the structure of proteins as randomly packed spheres that can evolve to accomplish a given function. When one sphere moves a certain way, this model can help scientists track its structural impact on the whole protein. Using this approach, the scientists addressed several questions that conventional models do not answer satisfactorily. Which types of 3D "architecture" are susceptible to allosteric effects? How many functional proteins with a similar architecture are they? How can these be modeled and evolved in a computer to offer predictions for drug design? Using theory and computer power, the team developed a new model that can predict the number of solutions, their 3D architectures and how the two relate to each other. Each solution can even be printed in a 3D printer to create a physical model. The model proposes a new hypothesis for allosteric architectures, introducing the concept that certain regions in the protein can act as levers. These levers amplify the response induced by binding a ligand and allow for action at a distance. This architecture is an alternative to the hinge and shear designs recognized in the past. The computational approach can also be used to study the relationship between co-evolution, mechanics, and function, while being open to many extensions in the future. This work involves a collaboration of EPFL's Physics of Complex Systems Laboratory with the University of California Santa Barbara and the Universidade Federal do Rio Grande do Sul in Brazil. It was funded by the National Science Foundation (NSF), the Swiss National Science Foundation (SNSF), and the Simons Foundation.


News Article | February 16, 2017
Site: www.eurekalert.org

The little striped zebrafish starts out as single big cell sitting on top of the yolk. During the next 3 days, cells divide and tissues move to give the fish its final shape. But how do tissues coordinate their often-complicated movements? The physical basis of tissue coordination in early zebrafish development is subject of a study by Carl-Philipp Heisenberg, Professor at the Institute of Science and Technology Austria (IST Austria) and his group, including first author and postdoc Hitoshi Morita, and colleagues at The Francis Crick Institute in London and the Max-Planck-Institute for the Physics of Complex Systems in Dresden. Until now, little has been known about how tissues coordinate their movement both temporally and spatially during development. In the study, published today in Developmental Cell, Heisenberg and co-authors investigated how tissues coordinate their movements and how the forces required for tissue movements are generated. In the paper, they show that cells at the surface are crucial for coordination. Carl-Philipp Heisenberg explains: "A reduction of surface tension by cells on the surface of the embryo is the key process that coordinates tissue movements at this timepoint." Tissue spreading is a key process both in development and disease, for example in wound healing. For a tissue, especially a complex tissue with several layers, to spread, it needs to simultaneously thin and expand. One example of such spreading is the so-called doming in the zebrafish embryo. During doming, the blastoderm, a tissue composed of surface epithelial cells and inner mesenchymal cells, thins and spreads over the yolk cell. Doming involves two tissue movements: the epithelial cell layer at the surface expands, and inner cells undergo intercalations thereby thinning and spreading the inner cell mass. In the present study, Heisenberg and his colleague asked how the two tissue movements - surface cell expansion and inner cell intercalation - coordinate their movements during blastoderm spreading. Combining theory and experiments, they show that surface cells, by undergoing active expansion, reduce the surface tension of the blastoderm. Strikingly, this loosening at the blastoderm surface not only triggers surface cell layer expansion, but also induces inner cell intercalation leading to inner cell layer thinning and spreading. Thus, the reduction in blastoderm surface tension represents the key process coordinating surface cell layer expansion with inner cell layer thinning and spreading during doming. First author Hitoshi Morita explains the significance of this study for understanding tissue spreading: "We have unravelled the force-generating processes that drive doming. Our study shows that by reducing its surface tension, the layer of epithelial cells simultaneously drives expansion and thinning of the blastoderm, and so coordinates these two processes. Coordinated tissue spreading is a universal mechanism by which embryos take shape. Understanding the force-generating mechanism is central for understanding the physical basis of embryo development. We have uncovered the key role surface cells play in this process."

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