This paper presents an overview of liquid crystal (LC) models of phase diagrams, phase transitions, self-assembly, interfaces, defects, and rheology and their integrated applications to biological mesophase materials and processes. Biological liquid crystals, classified into analogues (helicoidal plywoods), biopolymer solutions (in vitro DNA, polypeptides, collagen solutions) and in vivo LCs (membranes, silk, DNA), are discussed in terms of molecular characteristics and the symmetry of the thermodynamic phases. The thermodynamics and self-assembly of biological liquid crystals (BLCs) are discussed in terms of the Doi–Maier Saupe lyotropic model and its extensions to chiral phases, showing the role of excluded volume and chirality. The defect physics of BLCs is described using the Landau–de Gennes model of chiral and achiral nematostatics to identify (i) thermodynamic phases, and (ii) observed textures and defect lattices under confinement and flow. The rheology and flow properties of BLCs are described using the Leslie–Ericksen and the Landau–de Gennes models of nematodynamics. The applications of integrated thermodynamic/defect/rheology modeling to the experimental characterization of several BLCs, including collagen and DNA solutions, are shown to provide organizing principles and quantitative tools to establish the properties of these natural materials. The phase transitions, tactoidal spherulites, flow-birefringence in dilute solutions, and banded textures in sheared concentrated solutions of collagen show how the principles of LC physics operate in BLC materials. Drying and spreading drops of DNA solutions leading to the formation of nematic monodomain aligned along the contact line are shown to follow self-assembly structuring under the action of interfacial, bulk, and contact line torques. Finally modeling of spider and silkworm LC spinning is presented as an example of biological polymer processing, where a high performance fiber material is produced through a lyotropic LC protein solution. The concerted structuring action of capillary confinement, strong anchoring, and nematic flow leads to predictions in agreement with the reported textural transitions in the duct of spiders and silkworms. The quantitative description of BLC materials and processes using mesoscopic models provides another tool to develop the science and future biomimetic applications of these ubiquitous natural anisotropic soft materials.
生物学家早就发现了生物活细胞具有液晶的特性。生命过程中的物质的物理状态很大程度就是液晶态。 所谓生物膜是指细胞本身及周边以及大多数细胞质内的组成，包括叶绿体、细胞核、线粒体、高尔基体、液体泡和内质网都被一层“轨道”结构的膜所包裹，这种膜统称为生物膜。生物膜的主要成分是类脂化合物，其中磷脂占重要部分。磷脂分子是极性双亲分子，在水和油的界面上可以形成厚度约为一个分子长度的单层膜。在足够浓的水溶液中，两片单层面的疏水面可以合并形成厚度约为两个分子长度的双层膜。双层膜中的烃链有一定的排列有序性。
Kent State University, Summa Health System and IC-MedTech have developed a new paradigm in drug discovery based on the pharmacologic properties of Liquid Crystal Pharmaceuticals (LCPs). LCPs are a unique class of lyotropic liquid crystals that represent novel drug candidates for the treatment of a wide range of diseases. Representatives of this research project recently filed applications for two new patents: one for a new LCP-based anti-tumor drug called Tolecine™ and another for a formulation that combines Tolecine and another LCP, Apatone.
Tolecine is a new pre-clinical anti-tumor LCP that also has antiviral and antibacterial applications. It is tumor-cell selective and exhibits a strong anti-neoplastic activity (it counteracts abnormal proliferation of cells in a tissue or organ). In addition, it has been shown to be more effective than the current standard of care for herpes.
Apatone is a clinical phase investigational new drug for late-stage prostate cancer. It is currently under consideration for clinical study for potential applications such as augmentation of chemotherapy to allow lower, less toxic doses of common chemotherapeutic agents. Apatone is made from two non-toxic compounds, a liquid crystal compound and a sugar, that selectively bio-concentrate within cancer cells and produce a free radical. Formation of the strong, short lived free radical is a concentration driven intracellular reaction and therefore only takes place in cells with sufficient sugar concentrations (such as cancer cells). The reaction results in oxidative stress that weakens the targeted cells from within. It is carried out quickly only within the cancer cells, with no toxic reaction by-products that might harm adjacent healthy cells.
Atomic Force Microscope image of
nanostructured lyotropic liquid crystal
(Credit: Liquid Crystal Institute,
Kent State University)
Unlike other chemotherapy drugs, Tolecine and Apatone have low toxicity and do not target dividing cells. Instead, they are activated by inflammation that occurs in and around tumor cells, sparing healthy cells. Innovative, low-toxicity drugs such as Tolecine and Apatone provide new hope in the battle against cancer and other diseases. “LCPs are an untapped frontier from which many new, exciting treatments are now emerging”, says Dr. Chun-che Tsai, Kent State Professor of Chemistry, who created the new drugs with his colleagues.
Other attempts to develop targeted cancer-treatment strategies covered by TFOT include blockade of B-cells' proliferation in Leukemia, killing of dividing cells without harming the non-dividing cells using electrical fields, and killing lone cancer cells using alpha-particles' radiation.
Further information on Liquid Crystal Pharmaceuticals™, Tolecine and Apatone is available on Kent State University's Liquid Crystal Institute website and on IC-MedTech Inc. website.
http://thefutureofthings.com/news/1058/liquid-crystals-battle-cancer-and-other-diseases.html
Developing liquid crystal pharmaceuticals to fight cancer, other diseases
Kent State University, Summa Health System and IC-MedTech Inc. have taken steps toward that goal. Their collaborative efforts have yielded an innovative liquid crystal technology that offers the promise of new drugs which may more effectively manage cancer and other diseases.
Dr. Chun-che Tsai, Kent State professor of chemistry; Dr. Jim Jamison, manager of Urology, Obstetrics and Gynecology Core Basic Research Laboratory for Summa Health System; and Mr. Tom Miller, president of IC-MedTech Inc., a California-based biotechnology company, have developed a new paradigm in drug discovery based on the pharmacologic properties of liquid crystals called Liquid Crystal Pharmaceuticals™ or LCPs.
Recently, the team gathered at Kent State University’s Office of Technology Transfer to file applications for two new patents: one for a new LCP-based anti-tumor drug called Tolecine™ and another for a formulation that combines Tolecine™ and another LCP, Apatone®.
“The path-breaking discoveries of Dr. Tsai and his colleagues offer compelling proof of the value of university research and the enormous good that can come from collaborations between universities and the private sector,” says Kent State President Lester A. Lefton. “As Kent State researchers tackle cancer and a host of other real-world ills and issues, they are bringing their leading-edge knowledge and creativity to our students and playing a significant role in economic development.”
Though best known for their use in laptops, televisions and cell phones, liquid crystals also include families of organic substances that are essential for all life called lyotropic liquid crystals. Examples of lyotropic liquid crystals include DNA, proteins and cholesterol. LCPs are a unique class of lyotropic liquid crystals that represent novel drug candidates for the treatment of a wide range of diseases.
“Mother nature is the ultimate chemist,” says Tsai. “Although we use creative and sophisticated computer modeling techniques to screen for our candidate compounds, I’m always amazed at how nature puts it all together.”
The most recent research involving LCPs has yielded a new investigational anti-tumor drug called Tolecine™, a compound that also has antiviral and antibacterial applications. Created by Tsai, it has been shown to be even more effective than the current standard of care for herpes.
The team’s second patent application involves a formulation that combines Tolecine™ and another LCP, Apatone®, which attacks cancer cells via multiple pathways to offer improved efficacy. Apatone® has been successfully tested in more than 30 human tumor cell lines at Summa and in a Phase I/IIa clinical trial, which demonstrated a delaying effect in the progression of end-stage cancer patients. In addition, the FDA granted Apatone® orphan-drug status for the treatment of metastatic, or locally advanced, inoperable bladder cancer in August 2007.
Unlike other chemotherapy drugs, TolecineTM and Apatone®have low toxicity and do not target dividing cells. Instead, they are activated by inflammation that occurs in and around tumor cells, sparing healthy cells. “We want to kill cancer cells specifically without killing surrounding tissues,” says Jamison.
Innovative, low-toxicity drugs such as Tolecine™ and Apatone®provide new hope in the battle against cancer and other diseases in the next few years. “Research on LCPs provides a solid scientific foundation for generations of new drugs,” says Miller. Adds Tsai: “LCPs are an untapped frontier from which many new, exciting treatments are now emerging.” -Kent State University
http://www.huliq.com/33407/developing-liquid-crystal-pharmaceuticals-to-fight-cancer-other-diseases
Liquid Crystals in Biological Systems DOI: 10.1080/15421406608083293 Gordon T. Stewartab pages 563-580 Available online: 21 Mar 2007
There are several good theoretical reasons why matter in the liquid crystalline state should play a part in the structure of living tissue.
Many naturally-occurring substances exhibit paracrystalline behavior.
The most complex and some of the most reactive forms, the so-called cholesteric, are mainly or exclusively of natural origin.
No other formation of organic molecules possesses a comparable pattern of ordered structure in a state of flow.
This is not to say that liquid crystals must, therefore, be involved in living processes. It simply means that theory would fit fact, if facts were available.
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