Soft Matter and Biomaterials

DNA Smart materials

Dongsheng Liu
Department of Chemistry, Tsinghua University, Beijing 100084, China
The reversible responsiveness of DNA secondary structures to environmental stimuli has enable to facilitate responsive devices and materials based on pure DNA or hybrid systems. Based on sequence and structure design, we have prepared kinds of pure or hybrid DNA supramolecular hydrogels, which could be formed under physiological condition within a minute at room temperature and without using any organic solvents. By tailoring the length of “sticky ends” of DNA linker, mechanical property of the hydrogel could be varied from hundreds to thousands Pa (G’, storage modulus); we also found that the viability of cell in a 4 mm diameter hydrogel is nearly 100% after 24 hours incubation from top in plastic tubes. Additionally, the hydrogels show an excellent multiple responsiveness including pH, DNA restriction enzymes, protease digesting, temperature etc., which enable easy removal after cell culture. We believe these hydrogels have great potential in tissue engineering, especially for 3D cell printing. 

References:
1. J. Jin, S. Wang and D. Liu Advanced Materials, 2013, DOI: 10.1002/adma.201301175.
2. D. Liu, E. Cheng and Z. Yang, NPG Asia Mater., 2011, 3(10), 109.
3. Y. Xing, D. Liu, et al. Advanced Materials, 2011, 23, 1117.
4. E. Cheng, D. Liu, et al. Angew. Chem., Int. Ed. 2009, 48, 7660.
   
Chromoproteins offer new possibilities in optoelectronics

Pal Ormos1, L. Fabian1, A. Mathesz1, S.Valkai1, EK. Wolff2, A. Der1
1:Inst. Biophysics, Biological Rersearch Centre, Hung. Acad. of Sci., H-6726 Szeged, Hungary
2:Univ. Witten Herdecke, Inst Appl. Biotechnol. and Syst. Anal, D-58455 Witten, Germany
The capacity of complex biological functions of proteins originates in the complexity of their structure, and these special properties also offer completely novel applications in a number of emerging technological areas. Specifically, chromoproteins enable new applications that may profoundly advance optoelectronics. Example phenomena and applications will be presented on the light driven transmembrane proton pump bacteriorhodopsin. Upon absorption of light bacteriorhodopsin undergoes a sequence of photoreactions during which the color and refractive index change to a large extent and in a successive manner. This change can be utilized in optoelectronics applications. In appropriate optoelectronic devices it can be the active element in switching, router, logical arithmetical devices. In addition, by protein engineering techniques, the physical properties like color, crucial reaction rates can be modified to a large extent in a controlled manner. We demonstrate several applications in integrated optical devices: active control of biosensor devices by bacteriorhodopsin, ultrafast switching of optical signals, demonstration of logical operations performed in all optical optoelectronics devices, etc. 

References:
A Dér et al., Photochemistry and Photobiology 83 (2), 393–396 (2007)
L. Fabian Let al. Applied Physics Letters 97: 10.1063/1.3462940. (2010)
A. Mathesz et al., Biosensors and Bioelectronics, 46, 48-52 (2013)
    
Modeling Nanotoxicity: Large Scale Molecular Simulation of Nanoparticle-Protein Interactions and their Implications in Nanomedicine

Ruhong Zhou
Computational Biology Center, IBM Watson Research Center, Yorktown Heights, NY 10598 & Department of Chemistry, Columbia University, New York, NY 10027
Nanoscale particles have become promising materials in various biomedical applications, however, in order to stimulate and facilitate these applications, there is an urgent need for the understanding of their nanotoxicity and other related risks to human health. In this talk, I will discuss some of our recent molecular modeling work on nanotoxicity with IBM Blue Gene supercomputer. We show that carbon-based nanoparticles (carbon nanotubes, graphene nanosheets, and fullerenes) can interact and disrupt the structures and functions of many important proteins. The hydrophobic interactions between the carbon nanotubes and hydrophobic residues, particularly aromatic residues through the so-called  stacking interactions, are found to play key roles. Meanwhile, metallofullerenol Gd@C82(OH)22 is found to inhibit tumor growth and metastases (i.e. toxic to tumor cells) with both experimental and theoretical approaches. Graphene and graphene oxide nanosheets are shown to display antibacterial activities with surprising molecular mechanisms. These findings might provide a better understanding of “nanotoxicity” at the molecular level and help design better therapies with nanomedicine.
    
Evidence of disorder in biological molecules at single molecule level

Changbong Hyeon
Korea Institute for Advanced Study
Heterogeneity in biological molecules, resulting in molecule-to-molecule variations in their dynamics and function, is an emerging theme. Starting with several surprising observations with molecular heterogeneity from recent experiments, we will present how to analyze data with weakly broken ergodicity and what is the possible structural origin of the heterogeneities. Also, to elucidate the consequences of heterogeneous behavior manifested in the single molecule force spectroscopy, we propose an exactly solvable model based on the fluctuating bottleneck model. By fitting our analytical expressions to data from single molecule pulling experiments, we quantify the extent of disorder.
 
Soft Matter models of tissues:
Spreading and spontaneous motility of cellular aggregates

Francoise Brochard-Wyart, G. Beaune, D. Cuvelier, S. Douezan, S. Dufour, J. Dumond, D. Gonzalez, K. Guevorkian and T.V. Stirbat
Institut Curie-PCC Curie-UMR 168_ Paris France
Université Pierre et Marie Curie
We first describe the biomechanics of multicellular aggregates, a model system for tissues and tumors. We characterize the tissue mechanical properties (surface tension, elasticity, viscosity) by a new pipette aspiration technique. The aggregate exhibits a viscoelastic response but, unlike an inert fluid, we observe aggregate reinforcement with pressure, which for a narrow range of pressures results in pulsed contractions or “shivering”. We interpret this reinforcement as a mechanosensitive active response of the acto-myosin cortex.

  

We then describe the spreading of aggregates on rigid and soft substrates, varying both intercellular and substrate adhesion. We find both partial and complete wetting regimes. For the dynamics, we find a universal spreading law at short time, analogous to that of a viscoelastic drop. At long time, we observe a precursor film spreading around the aggregate. Depending on aggregate cohesion, this precursor film can be a dense cellular monolayer or consist of individual cells escaping from the aggregate The transition from “liquid” to “gas state” appears also to be present in the progression of a tumor from noninvasive to metastatic, known as the epithelial-mesenchymal transition. The dynamics of spreading results from a balance between active cellular driving forces and permeation of cells to enter into the film.

Finally we describe the motility of aggregates induced by chemical or rigidity gradients, or spontaneous: on soft substrate, the precursor film is unstable, leading to a symmetry breaking and a global motion of the aggregate, as a giant keratocyte (Figure). 

David Gonzalez-Rodriguez et al. (2012) Soft Matter Models of developing Tissues and Tumors. Science 338, 910; 1226418
S. Douezan and F. Brochard-Wyart (2012) Dewetting of cellular monolayers. EPJE, 35: 34, 201
David Gonzalez-Rodriguez et al. (2012) Opening of Macro apertures in Endothelial Cells. Phys. Rev. Lett. (108) 218105
Douezan S et al. (2012) Wetting transition of living drops induced by substrate rigidity. Soft Matter, 8: 4578-4583
Douezan S et al. (2011) Spreading dynamics and wetting of cellular aggregates. Proc. Nat. Acad. Sci (USA), 108: 7315
Guevorkian K et al. (2011) Shivering of model tissues under controlled aspiration. Proc. Nat. Acad. Sci (USA), 108: 1338
Guevorkian K et al. (2010) Aspiration of Biological Viscoelastic Drops. Phys. Rev. Lett. 104, 218101
 
Motion induced by osmotic pressure

  
Masao Doi 
Center of Soft Matter and Its Applications, Beihang University,
New Main Building Room H1114, No. 37 Xueyuanlu, Haidian, Beijing, China, 100191
Gradient of osmotic pressure generally induces a motion in solutions and gels. For example, if two solutions having different concentrations are separated by a semi-permeable which allows solvent to pass through but prohibits solute to pass through, a flow is induced in the solution which tends to equilibrate the chemical potential of solvent. Similarly if a salty solution is placed on top of a sheet of a hydrogel, the gel sheet bends temporarily, and then bends back. Here I discuss such motion using the Onsager principle, and demonstrate the utility of the principle in soft matter dynamics.

References:
[1] Soft Matter Physics, M. Doi, Oxford University Press (2013)
 
Self-powered kinesin-microtubule transport system

Junbai Li
Institute of Chemistry, CAS, Beijing 100190, China
Life lies in the movement. All the activities of the body, for example, muscle contraction, intracellular materials transport, the genetic material (DNA) replication and cell division, etc., are derived from the propulsion of motor proteins (kinesin, myosin, dynein) in the molecular level. With ATP as their 'fuel', motor proteins could effectively and directly convert chemical energy into mechanical energy and move directionally. Due to their high energy-conversion efficiency, biomotors have attracted great attentions and have been successfully applied in cargo transport, nanostructuring, surface imaging and sorting of protein assemblies. In all these systems, the supply of ATP is crucial. In this study, we constructed a 'fuel' generation system for motor protein (kinesin) based on creatine phosphate kinase (CPK) particles, which catalyzed the conversion of ADP and creatine phosphate to ATP. In the gliding motility assay, the velocity of microtubules (MT) increased with the increased concentration of ATP. Furthermore, MT-CPK particles complex was prepared and was successfully propelled on kinesin-modified surfaces using self-supplying ATP. The CPK particles here were not only acted as a fuel generation system, but also as a carrier for cargo transport. This self-powered kinesin-microtubule transport system would have great potential in local control of biomotors and other closed nanodevices.
 
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