Induced fit, conformational selection and independent dynamic segments: an extended view of binding events

Single molecule and NMR measurements of protein dynamics increasingly uncover the complexity of binding scenarios. Here we describe an extended conformational selection model which embraces a repertoire of selection and adjustment processes. Induced fit can be viewed as a subset of this repertoire, whose contribution is affected by the bond-types stabilizing the interaction and the differences between the interacting partners. We argue that protein segments whose dynamics are distinct from the rest of the protein ('discrete breathers') can govern conformational transitions and allosteric propagation that accompany binding processes, and as such may be more sensitive to mutational events. Additionally, we highlight the dynamic complexity of binding scenarios as they relate to events such as aggregation and signalling, and the crowded cellular environment.Comment: 9 pages, 2 Figures, 1 Table, 2 boxes, Trends in Biochemical Sciences 2010 October issue cover stor

Smart Computing and Sensing Technologies for Animal Welfare: A Systematic Review

Animals play a profoundly important and intricate role in our lives today. Dogs have been human companions for thousands of years, but they now work closely with us to assist the disabled, and in combat and search and rescue situations. Farm animals are a critical part of the global food supply chain, and there is increasing consumer interest in organically fed and humanely raised livestock, and how it impacts our health and environmental footprint. Wild animals are threatened with extinction by human induced factors, and shrinking and compromised habitat. This review sets the goal to systematically survey the existing literature in smart computing and sensing technologies for domestic, farm and wild animal welfare. We use the notion of \emph{animal welfare} in broad terms, to review the technologies for assessing whether animals are healthy, free of pain and suffering, and also positively stimulated in their environment. Also the notion of \emph{smart computing and sensing} is used in broad terms, to refer to computing and sensing systems that are not isolated but interconnected with communication networks, and capable of remote data collection, processing, exchange and analysis. We review smart technologies for domestic animals, indoor and outdoor animal farming, as well as animals in the wild and zoos. The findings of this review are expected to motivate future research and contribute to data, information and communication management as well as policy for animal welfare

Field-control, phase-transitions, and life's emergence

Instances of critical-like characteristics in living systems at each organizational level as well as the spontaneous emergence of computation (Langton), indicate the relevance of self-organized criticality (SOC). But extrapolating complex bio-systems to life's origins, brings up a paradox: how could simple organics--lacking the 'soft matter' response properties of today's bio-molecules--have dissipated energy from primordial reactions in a controlled manner for their 'ordering'? Nevertheless, a causal link of life's macroscopic irreversible dynamics to the microscopic reversible laws of statistical mechanics is indicated via the 'functional-takeover' of a soft magnetic scaffold by organics (c.f. Cairns-Smith's 'crystal-scaffold'). A field-controlled structure offers a mechanism for bootstrapping--bottom-up assembly with top-down control: its super-paramagnetic components obey reversible dynamics, but its dissipation of H-field energy for aggregation breaks time-reversal symmetry. The responsive adjustments of the controlled (host) mineral system to environmental changes would bring about mutual coupling between random organic sets supported by it; here the generation of long-range correlations within organic (guest) networks could include SOC-like mechanisms. And, such cooperative adjustments enable the selection of the functional configuration by altering the inorganic network's capacity to assist a spontaneous process. A non-equilibrium dynamics could now drive the kinetically-oriented system towards a series of phase-transitions with appropriate organic replacements 'taking-over' its functions.Comment: 54 pages, pdf fil

Programming DNA-Based Systems through Effective Molarity Enforced by Biomolecular Confinement

The fundamental concept of effective molarity is observed in a variety of biological processes, such as protein compartmentalization within organelles, membrane localization and signaling paths. To control molecular encountering and promote effective interactions, nature places biomolecules in specific sites inside the cell in order to generate a high, localized concentration different from the bulk concentration. Inspired by this mechanism, scientists have artificially recreated in the lab the same strategy to actuate and control artificial DNA-based functional systems. Here, it is discussed how harnessing effective molarity has led to the development of a number of proximity-induced strategies, with applications ranging from DNA-templated organic chemistry and catalysis, to biosensing and protein-supported DNA assembly

Multi-scale cellular engineering: From molecules to organ-on-a-chip.

Recent technological advances in cellular and molecular engineering have provided new insights into biology and enabled the design, manufacturing, and manipulation of complex living systems. Here, we summarize the state of advances at the molecular, cellular, and multi-cellular levels using experimental and computational tools. The areas of focus include intrinsically disordered proteins, synthetic proteins, spatiotemporally dynamic extracellular matrices, organ-on-a-chip approaches, and computational modeling, which all have tremendous potential for advancing fundamental and translational science. Perspectives on the current limitations and future directions are also described, with the goal of stimulating interest to overcome these hurdles using multi-disciplinary approaches

Collective motion of cells: from experiments to models

Swarming or collective motion of living entities is one of the most common and spectacular manifestations of living systems having been extensively studied in recent years. A number of general principles have been established. The interactions at the level of cells are quite different from those among individual animals therefore the study of collective motion of cells is likely to reveal some specific important features which are overviewed in this paper. In addition to presenting the most appealing results from the quickly growing related literature we also deliver a critical discussion of the emerging picture and summarize our present understanding of collective motion at the cellular level. Collective motion of cells plays an essential role in a number of experimental and real-life situations. In most cases the coordinated motion is a helpful aspect of the given phenomenon and results in making a related process more efficient (e.g., embryogenesis or wound healing), while in the case of tumor cell invasion it appears to speed up the progression of the disease. In these mechanisms cells both have to be motile and adhere to one another, the adherence feature being the most specific to this sort of collective behavior. One of the central aims of this review is both presenting the related experimental observations and treating them in the light of a few basic computational models so as to make an interpretation of the phenomena at a quantitative level as well.Comment: 24 pages, 25 figures, 13 reference video link

Plasticity of Cell Migration in Vivo and in Silico

Cell migration results from stepwise mechanical and chemical interactions between cells and their extracellular environment. Mechanistic principles that determine single-cell and collective migration modes and their interconversions depend upon the polarization, adhesion, deformability, contractility, and proteolytic ability of cells. Cellular determinants of cell migration respond to extracellular cues, including tissue composition, topography, alignment, and tissue-associated growth factors and cytokines. Both cellular determinants and tissue determinants are interdependent; undergo reciprocal adjustment; and jointly impact cell decision making, navigation, and migration outcome in complex environments. We here review the variability, decision making, and adaptation of cell migration approached by live-cell, in vivo, and in silico strategies, with a focus on cell movements in morphogenesis, repair, immune surveillance, and cancer metastasi

Designing stem cell niches for differentiation and self-renewal

Mesenchymal stem cells, characterized by their ability to differentiate into skeletal tissues and self-renew, hold great promise for both regenerative medicine and novel therapeutic discovery. However, their regenerative capacity is retained only when in contact with their specialized microenvironment, termed the stem cell niche. Niches provide structural and functional cues that are both biochemical and biophysical, stem cells integrate this complex array of signals with intrinsic regulatory networks to meet physiological demands. Although, some of these regulatory mechanisms remain poorly understood or difficult to harness with traditional culture systems. Biomaterial strategies are being developed that aim to recapitulate stem cell niches, by engineering microenvironments with physiological-like niche properties that aim to elucidate stem cell-regulatory mechanisms, and to harness their regenerative capacity in vitro. In the future, engineered niches will prove important tools for both regenerative medicine and therapeutic discoveries