Volume 37 Number 2 (May 2004), pp. 147–195

Cell-penetrating peptides: from inception to application

Due to a correction error at the Press stage the title of this paper was incorrectly published with the word ‘small’ included. The correct title is given above.

The publisher apologizes to the authors and readers for this error.

Elastin function is to endow vertebrate tissues with elasticity so that they can adapt to local mechanical constraints. The hydrophobicity and insolubility of the mature elastin polymer have hampered studies of its molecular organisation and structure-elasticity relationships. Nevertheless, a growing number of studies from a broad range of disciplines have provided invaluable insights, and several structural models of elastin have been proposed. However, many questions remain regarding how the primary sequence of elastin (and the soluble precursor tropoelastin) governs the molecular structure, its organisation into a polymeric network, and the mechanical properties of the resulting material. The elasticity of elastin is known to be largely entropic in origin, a property that is understood to arise from both its disordered molecular structure and its hydrophobic character. Despite a high degree of hydrophobicity, elastin does not form compact, water-excluding domains and remains highly disordered. However, elastin contains both stable and labile secondary structure elements. Current models of elastin structure and function are drawn from data collected on tropoelastin and on elastin-like peptides (ELPs) but at the tissue level, elasticity is only achieved after polymerisation of the mature elastin. In tissues, the reticulation of tropoelastin chains in water defines the polymer elastin that bears elasticity. Similarly, ELPs require polymerisation to become elastic. There is considerable interest in elastin especially in the biomaterials and cosmetic fields where ELPs are widely used. This review aims to provide an up-to-date survey of/perspective on current knowledge about the interplay between elastin structure, solvation, and entropic elasticity.

Optogenetics, the use of microbial rhodopsins to make the electrical activity of targeted neurons controllable by light, has swept through neuroscience, enabling thousands of scientists to study how specific neuron types contribute to behaviors and pathologies, and how they might serve as novel therapeutic targets. By activating a set of neurons, one can probe what functions they can initiate or sustain, and by silencing a set of neurons, one can probe the functions they are necessary for. We here review the biophysics of these molecules, asking why they became so useful in neuroscience for the study of brain circuitry. We review the history of the field, including early thinking, early experiments, applications of optogenetics, pre-optogenetics targeted neural control tools, and the history of discovering and characterizing microbial rhodopsins. We then review the biophysical attributes of rhodopsins that make them so useful to neuroscience – their classes and structure, their photocycles, their photocurrent magnitudes and kinetics, their action spectra, and their ion selectivity. Our hope is to convey to the reader how specific biophysical properties of these molecules made them especially useful to neuroscientists for a difficult problem – the control of high-speed electrical activity, with great precision and ease, in the brain.

Exposure to various chemicals, either due to occupation or lifestyle, is considered to be a major contributing factor to tumour formation in man (Higginson, 1969; Doll & Peto, 1981). An important and prevalent class of potent carcinogenic compounds present in the environment is polycyclic aromatic hydrocarbons (PAHs), which are found in various petroleum and combustion products derived from heat and power generation and motor vehicle exhausts (Baum, 1978). Furthermore, since PAHs are generally formed by pyrolysis of organic matters such as tobacco smoking and certain procedures of food preparation, the PAH exposure to humans is extensive.

In the very short time since magnetic resonance imaging (MRI) was born it has gained surprisingly rapid and enthusiastic acceptance and has speedily proliferated, particularly in the United States and Western Europe. Magnetic resonance imaging (MRI) has successfully challenged computed tomography (CT) in all areas of the body where respiratory motion does not degrade the image (Steinberg, 1986). Newer techniques using a multiplicity of approaches are starting to close the gap between CT and MRI, even in the upper abdomen where the effects of respiratory motion are most pronounced. Although MR is already widely clinically applied and is an accepted everyday diagnostic modality in most large medical centres in the United States, it is not a mature modality. It is rapidly evolving, with whole new areas opening to investigation which will vastly broaden its applications.

(Quart. Rev. Biophys. 12, 1, February 1979, page 51) contained several drafting errors. It should be replaced by the corrected version below.

1. INTRODUCTION 107

2. ORGANIZATION 108

3. THE MAIN GOALS 108

4. SCIENTIFIC ACTIVITIES 109

5. CONNECTION AND COOPERATION WITH OTHER ORGANIZATIONS 109

6. PUBLICATIONS 110

7. CLOSING REMARKS 110

8. HISTORICAL TABLES 111

9. APPENDIX: IUPAB STATUTES (as modified in Amsterdam, 1996) 115

The IUPAB was founded on 2 August 1961 in Stockholm as the International Organization of Pure and Applied Biophysics. The main goal of the Organization was to promote and organize international cooperation in biophysics and molecular biology and to encourage its development and practical application all over the world. Some detailed information on the foundation of the Union was published by A. K. Solomon (first Secretary General) in Quarterly Review of Biophysics.Another summary of the activity of IUPAB was prepared by R. D. Keynes(second Secretary General) in 1976.

Several functions of the animal body can take place in cell or tissue cultures with almost unreduced efficiency and precision. Functions, where only one cell type is involved, often do so, but also some differentiation steps where interactions between two or more cell types are clearly needed can take place in tissue culture (Saxén et al. 1968).

Most immune responses require collaboration between two or more cell types (Claman, Chaperon & Triplett, 1966; Miller & Mitchell, 1968; Feldmann & Nossal 1972c). Some of them can be easily induced in vitro but others cannot. Even when antibody responses can be induced in vitro their intensity varies a great deal. With some antigens and under some circumstances a response in vitro can be nearly as strong as one in vivo. A crude comparison can be derived from responses in vitro and in vivo to the same antigen, conjugate of hapten NIP and pneumococcal polysaccharide type III (NIP-SIll, Nakamura, Ray & Mäkelä, 1973).

Although viral protein structure and replication mechanisms have been explored extensively with X-ray crystallography, cryo-electron microscopy, and population imaging studies, these methods are often not able to distinguish dynamic conformational changes in real time. Single-molecule fluorescence resonance energy transfer (smFRET) offers unique insights into interactions and states that may be missed in ensemble studies, such as nucleic acid or protein structure, and conformational transitions during folding, receptor–ligand interactions, and fusion. We discuss the application of smFRET to the study of viral protein conformational dynamics, with a particular focus on viral glycoprotein dynamics, viral helicases, proteins involved in HIV reverse transcription, and the influenza RNA polymerase. smFRET experiments have played a crucial role in deciphering conformational changes in these processes, emphasising the importance of smFRET as a tool to help elucidate the life cycle of viral pathogens and identify key anti-viral targets.

Cell segregation caused by collective cell migration (CCM) is crucial for morphogenesis, functional development of tissue parts, and is an important aspect in other diseases such as cancer and its metastasis process. Efficiency of the cell segregation depends on the interplay between: (1) biochemical processes such as cell signaling and gene expression and (2) physical interactions between cells. Despite extensive research devoted to study the segregation of various co-cultured systems, we still do not understand the role of physical interactions in cell segregation. Cumulative effects of these physical interactions appear in the form of physical parameters such as: (1) tissue surface tension, (2) viscoelasticity caused by CCM, and (3) solid stress accumulated in multicellular systems. These parameters primarily depend on the interplay between the state of cell–cell adhesion contacts and cell contractility. The role of these physical parameters on the segregation efficiency is discussed on model systems such as co-cultured breast cell spheroids consisting of two subpopulations that are in contact. This review study aims to: (1) summarize biological aspects related to cell segregation, mechanical properties of cell collectives, effects along the biointerface between cell subpopulations and (2) describe from a biophysical/mathematical perspective the same biological aspects summarized before. So that overall it can illustrate the complexity of the biological systems that translate into very complex biophysical/mathematical equations. Moreover, by presenting in parallel these two seemingly different parts (biology vs. equations), this review aims to emphasize the need for experiments to estimate the variety of parameters entering the resulting complex biophysical/mathematical models.